Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 73 records · Page 4Linked to original sources

PubMed2001

APOE polymorphism and the hypertriglyceridemic effect of dietary sucrose.

BACKGROUND: The E4 allele of the apolipoprotein gene (APOE) is associated with a greater serum cholesterol response to dietary changes in fat and cholesterol. However, less is known about the interaction between APOE polymorphism and other macronutrients in the diet. OBJECTIVE: We evaluated the interaction between APOE polymorphism and dietary fat and carbohydrate, particularly sucrose, in relation to serum lipid concentrations. DESIGN: A total of 284 men and 130 women with coronary artery disease (mean age: 61 y; range: 33-74 y) participated in the cross-sectional EUROASPIRE study. Serum lipids and fatty acids in cholesteryl esters (CEs) were measured and APOE genotypes were determined. Dietary intake was examined by using a 4-d food record. RESULTS: Patients were grouped by APOE genotype: E2 (E2/E2 and E2/E3; n = 21), E3 (E3/E3; n = 245), and E4 (E4/E2, E4/E3, and E4/E4; n = 148). Patients with the E2 allele had lower LDL-cholesterol concentrations and tended to have higher triacylglycerol concentrations than did patients with the E3 or E4 allele; concentrations were not significantly different between the last 2 groups. In regression analysis, significant predictors of serum triacylglycerol were the interaction between sucrose intake and the E2 allele, proportion of n-3 fatty acids in CEs, body mass index, and diabetes. A high sucrose intake was associated with high triacylglycerol concentrations only in patients with the E2 allele. Interaction between saturated fat intake and the E2 allele, proportion of linoleic acid in CEs, and fiber intake predicted serum cholesterol. CONCLUSION: Coronary artery disease patients with the E2 allele will likely have a greater triacylglycerol response to high dietary sucrose intakes than will patients with the E3 or E4 allele.

Adult↗

PubMed2001

Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general population.

Adipose Tissue↗

PubMed2001

Cardiovascular risk factors associated with insulin resistance cluster in families with early-onset coronary heart disease.

Coronary heart disease (CHD) is a multifactorial disease caused by environmental and genetic factors. CHD clusters in families, but it is not known whether susceptibility to early-onset CHD is associated with the clustering of cardiovascular risk factors. Therefore, we determined the levels of cardiovascular risk factors among siblings with and without severe early-onset CHD drawn from 101 Finnish families. Probands with CHD, compared with their siblings without CHD, had, respectively, higher 2-hour insulin levels (475.7 versus 331.8 pmol/L, P=0.011) and 2-hour insulin areas (796.2 versus 640.4 pmol/L per hour, P=0.031) in an oral glucose tolerance test, lower high density lipoprotein cholesterol levels (1.22 versus 1.42 mmol/L, P=0.001), higher total triglyceride levels (1.91 versus 1.68 mmol/L, P=0.018), higher very low density lipoprotein triglyceride levels (1.25 versus 1.06 mmol/L, P=0.011), and higher fibrinogen levels (3.8 versus 3.4 g/L, P= 0.008). No significant differences were found in cardiovascular risk factors between affected siblings and probands with CHD. Environmental or lifestyle factors did not differ between siblings with or without early-onset CHD. We conclude that cardiovascular risk factors associated with the insulin resistance syndrome (hyperinsulinemia, low high density lipoprotein cholesterol, high total and very low density lipoprotein triglycerides, and high fibrinogen) are likely to contribute indirectly to early-onset CHD.

Adult↗

PubMed2001

A major gene effect on fasting insulin and insulin sensitivity in familial combined hyperlipidemia.

The most common inherited dyslipidemia, familial combined hyperlipidemia (FCHL), is associated with insulin resistance. Whether insulin sensitivity in these families is inherited is not known. Therefore, we investigated the inheritance of insulin sensitivity in 352 nondiabetic family members from 37 families with FCHL, 105 of whom had undergone testing using the hyperinsulinemic-euglycemic clamp technique for the measurement of insulin sensitivity. First, complex segregation analysis of fasting insulin levels (both unadjusted and age-, age(2)-, and BMI-adjusted) was used for modeling of the variance in fasting insulin levels. In these analyses, Mendelian codominant inheritance (P = 0.320 for unadjusted and P = 0.295 for adjusted insulin values) was not rejected over the most general model and fit the data significantly better than the sporadic model (P < 0.001). Polygenic and environmental models were rejected (P < 0.001). The Mendelian codominant model explained 44 and 45% of the variance in unadjusted and adjusted fasting insulin levels, respectively. The proposed genotypes of this locus, based on segregation analysis, were associated with directly measured insulin sensitivity in 105 FCHL family members who underwent the hyperinsulinemic-euglycemic clamp (P < 0.001). These results provide evidence for a major gene regulating insulin sensitivity in FCHL families. Possible pleiotropic effects of this insulin sensitivity locus on dyslipidemias in FCHL remain to be elucidated.

Adult↗

PubMed2001

New amino acid substitutions in the IRS-2 gene in Finnish and Chinese subjects with late-onset type 2 diabetes.

We investigated the significance of the variants of the IRS-2 gene in patients with type 2 diabetes. The entire coding part of the IRS-2 gene was screened by single-strand conformation polymorphism analysis in 40 Chinese and 40 Finnish patients with late-onset type 2 diabetes. The association of the variants of the IRS-2 gene with type 2 diabetes was studied in 85 Finnish diabetic patients and 82 Finnish control subjects and in 100 Chinese diabetic patients and 85 Chinese control subjects. The four variants predicting structural changes in the insulin receptor substrate (IRS)-2 protein included an insertion of AAC (Asn) in the Asn repeat sequence centered around codons 29-36 (allele frequencies of 0 vs. 0.6% and 1.5 vs. 0%), the Ala157Thr substitution (0 vs. 0% and 0.5 vs. 0%), the Leu647Val substitution (0.6 vs. 0% and 0 vs. 0%), and the Gly1057Asp polymorphism (31 vs. 31% and 35 vs. 30%) (P = NS for all comparisons). Furthermore, six silent variants were observed (CGC147CGG, CCC155CCG, GCC156GCT, AGT723AGC, TGT816TGC, and CCC829CCT). The Gly1057Asp polymorphism was not associated with insulin resistance or impaired insulin secretion in Finnish subjects with normal glucose tolerance (n = 295) or impaired glucose tolerance (n = 38). These data indicate that structural variants of the IRS-2 gene were uncommon in Finnish and Chinese patients with type 2 diabetes. Thus, the variants in the coding part of the IRS-2 gene are unlikely to have a major role in the development of type 2 diabetes in Finnish or Chinese subjects.

Age of Onset↗

PubMed2001

Insulin resistance syndrome predicts coronary heart disease events in elderly type 2 diabetic men.

OBJECTIVE: To investigate whether cardiovascular risk factors cluster with hyperinsulinemia in elderly type 2 diabetic subjects and, if so, whether this clustering predicts coronary heart disease (CHD) events during a 7-year follow-up. RESEARCH DESIGN AND METHODS: Clustering of cardiovascular risk factors was analyzed by factor analysis. Cox regression models were used to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) during a 7-year follow-up in 229 type 2 diabetic subjects aged 65-74 years. RESULTS: There were 70 CHD events (21 in men and 49 in women) during the follow-up period. In diabetic men, components of the insulin resistance syndrome (IRS) loaded on Factor 1 (the insulin resistance factor), which reflected high fasting insulin, obesity (high BMI), central obesity (high waist-to-hip ratio), high total triglycerides, and a short duration of diabetes. Only this IRS factor predicted CHD events in multivariate Cox regression analysis (hazard ratio [HR] 1.71, 95% CI 1.08-2.71, P = 0.022). In diabetic women, components of IRS loaded on two factors, none of which predicted CHD events. In women, only Factor 4, characterized by advanced age, left ventricular hypertrophy on electrocardiogram, high alcohol consumption, high systolic blood pressure, and albuminuria, predicted CHD events in multivariate Cox regression analysis (1.34, 1.03-1.74, P = 0.03). CONCLUSIONS: IRS is a risk factor for CHD in elderly type 2 diabetic men.

Aged↗

PubMed2001

Insulin resistance and its impact on the approach to therapy of type 2 diabetes.

Insulin resistance is a core defect in Type 2 diabetes, occurring in peripheral organs (skeletal muscle and adipose tissue) leading to decreased glucose uptake and utilisation and in liver leading to increased hepatic glucose production. As long as the beta-cell can compensate for this by producing more insulin, glucose tolerance remains normal. However, as insulin resistance worsens, the beta-cell starts to fail to compensate leading to impaired glucose tolerance and then frank diabetes. The exact pathophysiology of insulin resistance is not clear but it probably involves a combination of genetic and environmental factors. These factors may result in changes in the number of insulin receptors, their affinity for insulin or a defect in post-receptor signalling or a combination of these. Insulin resistance also affects lipid metabolism such that there is increased production of triglycerides from the liver, which in turn both amplifies insulin resistance and exacerbates atherogenesis. The promotion of atherosclerosis by insulin resistance means that patients with Type 2 diabetes are at particularly high risk of cardiovascular disease. Therefore, treatment of insulin resistance with thiazolidinediones has the potential to offer improvements both in glycaemic control and in cardiovascular events.

Diabetes Mellitus, Type 2↗

PubMed2000

Evidence for central alpha(2)-adrenergic modulation of rat pineal melatonin synthesis.

This study was performed to distinguish central and peripheral alpha(2)-adrenoceptors in the inhibition of rat pineal melatonin synthesis. The rats received lipo- or hydrophilic alpha(2)-adrenoceptor ligand injections at middark; after 1 or 2 h the pineal melatonin contents were measured. The lipophilic agonist medetomidine (100 microg/kg s.c.) suppressed the melatonin contents significantly, while the hydrophilic agonists ST-91 and p-aminoclonidine (10 or 100 microg/kg i.v.) did not. The suppression by medetomidine was counteracted by the lipophilic antagonist yohimbine (0.3-3.0 mg/kg i.p.) but not by the hydrophilic antagonist L-659,066 (1-10 mg/kg i.v.). In conclusion, the suppression of nocturnal melatonin synthesis by alpha(2)-adrenoceptor agonists is mainly of central origin.

Adrenergic alpha-Agonists↗

PubMed2000

Bright light exposure of a large skin area does not affect melatonin or bilirubin levels in humans.

BACKGROUND: Light treatment through the eyes is effective in alleviating the symptoms of some psychiatric disorders. A recent report suggested that skin light exposure can affect human circadian rhythms. Bilirubin can serve as a hypothetical blood-borne mediator of skin illumination into the brain. We studied whether bright light directed to a large body area could suppress the pineal melatonin secretion or decrease serum total bilirubin in conditions that could be used for therapeutic purposes. METHODS: Seven healthy volunteers participated in two consecutive overnight sessions that were identical except for a light exposure on the chest and abdomen in the second night from 12:00 AM to 6:00 AM (10,000-lux, 32 W/m(2) cool white for six subjects and 3000-lux, 15 W/m(2) blue light for one subject). Hourly blood samples were collected from 7:00 PM to 7:00 AM for melatonin radioimmunoassays. Bilirubin was measured by a modified diazo method in blood samples taken at 12:00 AM and 6:00 AM and in urine samples collected from 7:00 PM to 11:00 PM and from 11:00 PM to 7:00 AM. RESULTS: The skin light exposure did not cause any significant changes in serum melatonin or bilirubin levels. The excretion of bilirubin in urine was also the same in both sessions. CONCLUSIONS: Significant melatonin suppression by extraocular light does not occur in humans. Robust concentration changes of serum total bilirubin do not have a role in mediating light information from the skin to the central nervous system.

Abdomen↗

PubMed2000

Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland.

Coronary heart disease (CHD) is a complex disorder constituting a major health problem in Western societies. To assess the genetic background of CHD, we performed a genomewide linkage scan in two study samples from the genetically isolated population of Finland. An initial study sample consisted of family material from the northeastern part of Finland, settled by a small number of founders approximately 300 years ago. A second study sample originated from the southwestern region of Finland, settled approximately 2,000 years ago. Families were ascertained through probands exhibiting premature CHD, defined as >50% stenosis of at least two coronary arteries at a young age, as verified by coronary angiography. Both study samples and the pooled data set provided evidence for linkage in two chromosomal regions. A region on chromosome 2q21.1-22 yielded two-point LOD scores of 3.2, 1.9, and 3.7, in the affected sib-pair (ASP) analyses of the northeastern, southwestern, and pooled study samples. The corresponding multipoint maximum-likelihood scores (MLSs) for these three study samples were 2.4, 1.3, and 3.0. In addition, a region on chromosome Xq23-26 resulted in two-point LOD scores of 1.9, 3.5, and 2.9 and in multipoint MLSs of 3.4, 3.1, and 2.5, respectively. In conclusion, this study identifies two loci likely to contribute to premature CHD: one on chromosome 2q21.1-22 and another on chromosome Xq23-26.

Age of Onset↗

PubMed2000

Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty.

Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl of DOTMA:DOPE liposomes. Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia.

Adult↗

PubMed2000

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease.

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.

Adult↗

PubMed2000

Cardiovascular risk factors clustering with endogenous hyperinsulinaemia predict death from coronary heart disease in patients with Type II diabetes.

AIMS/HYPOTHESIS: Information on the association of hyperinsulinaemia with coronary heart disease (CHD) in patients with Type II (non-insulin-dependent) diabetes is limited and controversial. Therefore, we carried out a prospective study to examine the predictive value of fasting plasma insulin and "hyperinsulinaemia cluster" with regard to the risk of CHD mortality. METHODS: At baseline risk factors for CHD were determined in 902 patients aged 45 to 64 years with Type II diabetes not treated by insulin (499 men and 403 women). These patients were followed up to 7 years for CHD mortality. RESULTS: Coronary heart disease mortality (16.2% in men, 9.2% in women) increased significantly in men with increasing plasma insulin tertiles (p = 0.006) and in both sexes combined (p = 0.010) but not in women (p = 0.090). The predictive value of hyperinsulinaemia with regard to death from CHD was independent of conventional cardiovascular risk factors but not of risk factors clustering with hyperinsulinaemia. By applying factor analysis and principal component analysis we showed that "hyperinsulinaemia cluster" (a factor having high positive loadings for body mass index, triglycerides and insulin; and a high negative loading for high-density lipoprotein cholesterol) was predictive of death from CHD in patients with Type II diabetes (hazard ratio with 95% confidence intervals 1.43 (1.18, 1.73), p < 0.001). CONCLUSION/INTERPRETATION: Our results support the notion that cardiovascular risk factors clustering with endogenous hyperinsulinaemia increase the risk of death from CHD in patients with Type II diabetes not treated with insulin.

Age Factors↗

PubMed2000

Impaired insulin secretion in non-diabetic offspring of probands with latent autoimmune diabetes mellitus in adults.

AIMS/HYPOTHESIS: This study was undertaken to investigate metabolic and genetic characteristics of latent autoimmune diabetes in adults (LADA). METHODS: We evaluated insulin secretory capacity with oral and intravenous glucose tolerance tests (early insulin response) and hyperglycaemic clamp (insulin secretory capacity) and the rates of whole body glucose uptake with the euglycaemic clamp, HLA-DQB1 genotypes (time-resolved fluorescence) and islet cell antibodies (ICA) (immunofluorescence) and antibodies to glutamic acid decarboxylase (GAD) (radio-immunoprecipitation) in 36 non-diabetic offspring (LADA-offspring) of patients with Type II (non-insulin-dependent) diabetes mellitus who tested positive for ICA and/or GAD antibodies during the 10-year follow-up from the diagnosis and in 19 healthy control subjects without a family history of diabetes. RESULTS: The early insulin response during the first 10 min of an intravenous glucose tolerance test was about 40% lower in the LADA-offspring than in the control group (p = 0.008). Insulin secretory capacity in the hyperglycaemic clamp was also about 30% lower in the LADA-offspring (p = 0.048). The rates of whole body glucose uptake were similar in both groups. The frequency of low risk HLA-DQB1 genotypes was higher in the LADA-offspring than among Finnish healthy blood donors (p = 0.033). The risk conferring genotypes were associated with the lowest tertile of insulin secretory capacity in the LADA-offspring (p = 0.032). There were no associations between the autoantibodies and early insulin response or insulin secretory capacity within the study groups. CONCLUSION/INTERPRETATION: We conclude that LADA is a familial disease involving most likely gene defects leading to a slow progressive beta-cell destruction and insulin deficiency.

Adipose Tissue↗

PubMed2000

Mouse hexokinase II gene: structure, cDNA, promoter analysis, and expression pattern.

In mammalian tissues, the phosphorylation of intracellular glucose to glucose-6-phosphate (Glu-6-P) is facilitated by four distinct hexokinase (HK) isoenzymes, designated as HKI-IV. Because of the role of HKII as a leading glycolytic enzyme in insulin-sensitive tissues such as skeletal muscle, heart, and adipose tissue, defects in HKII function could contribute to the development of insulin resistance and perhaps Type 2 diabetes. As a first step towards elucidation of the physiological role of HKII in insulin resistance and type 2 diabetes using mouse knock-out models, we determined the genomic structure, sequence of the cDNA and of 4.8 kb of the 5' regulatory region, and tissue-specific expression of the mouse HKII gene. The gene comprises 18 exons that span approximately 50 kb of DNA. Nucleotide sequence of the proximal promoter revealed a number of conserved putative transcription factor binding motifs. We also found numerous repeat elements throughout the mouse HKII gene. The mouse HKII cDNA is approximately 5.5 kb in length and contains an open reading frome of 2751 bp encoding a protein of 917 amino acids. The mouse HKII gene is predominantly expressed in skeletal muscle, heart, and adipose tissue. The transcription initiation and polyadenylation sites for the mouse HKII mRNA were similar to those of the rat and human genes.

Animals↗

PubMed2000

The Pro12A1a substitution in the peroxisome proliferator activated receptor gamma 2 is associated with an insulin-sensitive phenotype in families with familial combined hyperlipidemia and in nondiabetic elderly subjects with dyslipidemia.

Dyslipidemias and insulin resistance often present simultaneously, as in familial combined hyperlipidemia (FCHL), and therefore may have a common genetic background. In our previous study the Pro12A1a substitution of peroxisome proliferator receptor gamma 2 (PPARgamma2) associated with insulin sensitivity, low body mass index (BMI) and high-density lipoprotein (HDL) cholesterol levels. In this study, we investigated the role of this substitution in dyslipidemias. Therefore, 228 nondiabetic members of FCHL families and 866 nondiabetic elderly subjects with (n=217) and without dyslipidemia (n=649) were genotyped. The allele frequencies of the Pro12A1a substitution did not differ between elderly subjects with or without dyslipidemia or 27 probands with FCHL. However, this substitution was associated with low fasting insulin levels both in FCHL family members (P = 0.036 adjusted for gender and age) and elderly subjects with dyslipidemia (P=0.050) but not in elderly subjects without dyslipidemia (P=0.080). In addition, the Ala12 allele of PPARgamma2 was associated with low BMI (P= 0.034) and low total triglycerides (P=0.027), and increased HDL-cholesterol (P < 0.001) in elderly subjects with dyslipidemia (n=299) but not among any other study groups. We conclude that the Ala12 isoform of PPARgamma2 ameliorates the insulin resistance and unfavorable lipid and lipoprotein profiles in FCHL and hyperlipidemic elderly subjects.

Adult↗

PubMed2000

Antihypertensive drugs as predictors of type 2 diabetes among subjects with impaired glucose tolerance.

AIMS: to examine the incidence rate of progression to Type 2 diabetes and baseline prognostic risk factors, focusing on hypertension and antihypertensive medication, in a cohort (n=207) with impaired glucose tolerance (IGT). METHODS: after 2 and 4.6 (1. 9-6.4) years new cases of diabetes were diagnosed by the oral glucose tolerance test (OGTT). Hypertension (BP 160/95 or antihypertensive medication) was included in multiple regression analyses to assess the effect of risk factors on the development of diabetes. RESULTS: diabetes developed in 32 subjects (19%), an incidence of 41/1000 (95% CI 28-57/1000) person-years. In univariate analyses, progression to diabetes was associated with a high (>9.0 mmol/l) 2-h OGTT value (P=0.008), a high fasting insulin (>12.0 mU/l) level (P=0.000), a high triglyceride (>/=1.3 mmol/l) level (P=0.028), a high BMI (>/=28.0 kg/m(2)) (P=0.013) and hypertension (P=0.003). The risk for the development of diabetes was not increased in hypertensive subjects without antihypertensive medication compared with normotensive subjects (OR 0.8, 95% CI 0.3-2. 6). However, it was increased in subjects with on medication, especially diuretics alone or in combination with other drugs. Hypertensive subjects on diuretics had higher levels of fasting insulin and triglycerides and higher BMIs at baseline than normotensive subjects. After adjustment for 2-h OGTT, fasting insulin, triglycerides and BMI, the OR for diabetes was 7.7 (95% CI 2.1-28.2) in hypertensive subjects using diuretics alone or in combination with other drugs and 2.6 (95% CI 1.0-6.7) in those using other drugs compared with normotensive subjects. The OR of diabetes corresponding to a one-unit increase in the 2-h OGTT concentration was 2.5 (95% CI 1.6-4.0) in the whole cohort. CONCLUSIONS: the rate of progression from IGT to Type 2 diabetes in this population was similar to that seen in other studies among Caucasian populations. The use of antihypertensive medication, especially diuretics, and a high 2-h OGTT level were significant predictors of subsequent deterioration to diabetes.

Antihypertensive Agents↗

PubMed2000

Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects.

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10y follow-up study. DESIGN: Controlled 10y follow-up study with baseline, 5 and 10y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA1c. Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P=0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P= 0.060, mean +/- s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Anthropometry↗