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Matti Uusitupa

Publications and source records attributed to Matti Uusitupa.

53 records · Page 3Linked to original sources
PubMed2003

The Leu7Pro polymorphism of the neuropeptide Y gene regulates free fatty acid metabolism.

The Leu7Pro polymorphism in the signal peptide of the preproneuropeptide Y (NPY) has been associated with dyslipidemias and free fatty acid (FFA) levels during exercise. The association of this polymorphism with insulin sensitivity has not been studied. In this study, the Leu7Pro polymorphism was determined in 2 groups of nondiabetic middle-aged subjects (n = 266 and n = 295). Insulin sensitivity was measured with the hyperinsulinemic euglycemic clamp (n = 266) or with an intravenous glucose tolerance test (IVGTT, n = 295). First-phase insulin secretion was determined as insulin area under the curve (AUC) during the first 10 minutes of the IVGTT. FFAs were measured both in the fasting state and during the hyperinsulinemic clamp. The Leu7Pro polymorphism of the NPY gene was not associated with the rates of whole body glucose uptake, insulin sensitivity index, insulin secretion during the IVGTT, or insulin AUC during the oral glucose tolerance test. However, the Pro7 allele was associated with low FFA levels both in the fasting state (P =.043) and during the hyperinsulinemic clamp (P =.003). In conclusion, the Leu7Pro polymorphism of the NPY gene associates with alterations in FFA metabolism but does not have an impact on insulin sensitivity, insulin secretion, or glucose metabolism.

Alleles↗
PubMed2003

Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial.

Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle. The Finnish Diabetes Prevention Study (DPS) is the first individually randomized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects. We randomly assigned 522 (172 men, 350 women) middle-aged (mean age 55 yr), overweight (mean body mass index 31 kg/m(2)) subjects with impaired glucose tolerance either to the lifestyle intervention or control group. Each subject in the intervention group received individualized counseling aimed at reducing weight and intake of total and saturated fat, and increasing intake of fiber and physical activity. An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters. The mean (+/- SD) weight reduction from baseline to year 1 and to year 2, respectively, was 4.2 +/- 5.1 kg and 3.5 +/- 5.5 in the intervention group and 0.8 +/- 3.7 kg and 0.8 +/- 4.4 in the control group (P < 0.001 between the groups). At the time of first analysis of the outcome data the mean duration of follow-up was 3.2 yr. The risk of diabetes was reduced by 58% (P < 0.001) in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made. In conclusion, the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects.

Adult↗
PubMed2003

Long-term improvement in insulin sensitivity by changing lifestyles of people with impaired glucose tolerance: 4-year results from the Finnish Diabetes Prevention Study.

Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance (IGT). However, it is unknown whether this is due to improved insulin sensitivity or insulin secretion. We investigated at baseline insulin sensitivity and insulin secretion applying frequently sampled intravenous glucose tolerance test (FSIGT) in 87 of 101 obese middle-aged subjects with IGT randomized into an intervention or a control group in the Finnish Diabetes Prevention Study. FSIGT was repeated after 4 years in 52 people. There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups. The 4-year weight and waist circumference decreases were greater in the intervention than in the control group (P = 0.043 and P = 0.025, respectively). At 4-year examination, insulin sensitivity (Si) tended to be higher in the intervention group (the difference between the mean values 36%; P = 0.067, and P = 0.136 after adjustment for age, sex, BMI, and baseline Si value). There was strong correlation between the 4-year changes in Si and weight (r = -0.628 and r = -0.710, for intervention and control groups; P < 0.001 for both). In the entire group, Si improved by 64% in the highest tertile of weight loss but deteriorated by 24% in those who gained weight (lowest tertile). Acute insulin response declined significantly in the control group. In conclusion, Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT. Insulin secretion remained constant for years in individuals with IGT who were able to lose weight.

Adult↗
PubMed2003

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.

Analysis of Variance↗
PubMed2003

The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity.

OBJECTIVE: To describe the 1) lifestyle intervention used in the Finnish Diabetes Prevention Study, 2) short- and long-term changes in diet and exercise behavior, and 3) effect of the intervention on glucose and lipid metabolism. RESEARCH DESIGN AND METHODS: There were 522 middle-aged, overweight subjects with impaired glucose tolerance who were randomized to either a usual care control group or an intensive lifestyle intervention group. The control group received general dietary and exercise advice at baseline and had an annual physician's examination. The subjects in the intervention group received additional individualized dietary counseling from a nutritionist. They were also offered circuit-type resistance training sessions and advised to increase overall physical activity. The intervention was the most intensive during the first year, followed by a maintenance period. The intervention goals were to reduce body weight, reduce dietary and saturated fat, and increase physical activity and dietary fiber. RESULTS: The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group, respectively. Measures of glycemia and lipemia improved more in the intervention group. CONCLUSIONS: The intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, and clinical and biochemical parameters and reduced diabetes risk. This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system.

Diabetes Mellitus, Type 2↗
PubMed2002

Short-term LDL cholesterol-lowering efficacy of plant stanol esters.

BACKGROUND: The short-term cholesterol-lowering efficacy of plant stanol esters has been open to debate, and the data from different clinical studies with hypercholesterolemic subjects are variable, partly due to lack of systematic studies. Therefore, we investigated the time in days needed to obtain the full cholesterol-lowering effect of stanol esters in hypercholesterolemic subjects. METHODS: Eleven mildly to moderately hypercholesterolemic subjects consumed stanol ester margarine (2.0 g/day of stanols) as a part of their habitual diet for 14 days and the changes in serum lipid values were measured three times at 4, 8 and 15 days after the initiation of test margarine consumption (0 day). The returning of serum lipid concentrations to baseline was measured two times after 2 or 3 days and after 7 days of the end of the test margarine consumption. RESULTS: Serum LDL cholesterol concentrations were reduced from 0 day (4.51 +/- 0.66 mmol/l) by 3.5% (P = ns), 9.9% (p < 0.05) and 10.2% (P < 0.05) at 4, 8 and 15 days, respectively. Serum campesterol/total cholesterol ratio, an indirect marker of intestinal cholesterol absorption, was significantly reduced on day 4 already. After ending the stanol ester use serum cholesterol concentrations began to return rapidly and after 7 days serum LDL cholesterol was 5.3% less than the initial value (P = ns). CONCLUSION: The specific effect of plant stanol esters on serum LDL cholesterol can fully be obtained within 1-2 weeks of the use of plant stanol ester-enriched margarine.

Adult↗
PubMed2002

Iris transluminance in type 2 diabetes.

PURPOSE: Cross-sectional analysis of iris transluminance in type 2 diabetic patients compared with control subjects, all followed in a cohort study. METHODS: A cohort consisting of a well-characterized group of 82 type 2 diabetic patients were followed for 10 years after diagnosis, as were 125 control subjects. The prevalence of iris transluminance was determined by transscleral transillumination and by grading of black-and-white positive prints at the 10-year examination. The frequency of diabetic retinopathy was prospectively determined by grading of fundus photographs at baseline and after five and 10 years. RESULTS: Iris transluminance was found in 27% of diabetic patients and 8.0% of control subjects (P = 0.001). The diabetic patients with more severe and short-term retinopathy more commonly had abnormal iris transluminance than those with no or only mild retinopathy (P < 0.05). Iris transluminance was not associated with intraocular pressure or glycemic control. CONCLUSIONS: In type 2 diabetic patients, abnormal iris transluminance tended to associate with more severe and short-term retinopathy. Therefore we assume that hypoxia is responsible for the defects in the pigment layer of the iris. Thus, abnormal iris transluminance may serve as a marker for rapidly progressive retinopathy.

Diabetes Mellitus, Type 2↗
PubMed2002

Anthropometry, bioelectrical impedance and dual-energy X-ray absorptiometry in the assessment of body composition in elderly Finnish women.

In this study, the bioelectrical impedance analysis (BIA), skinfold thickness measurement (STM) and dual-energy X-ray absorptiometry (DXA), as a reference method, were compared with each other in the assessment of body composition in elderly (62-72-year-old) Finnish women (n=93). BIA had better agreement with DXA in the assessment of fat free mass (FFM, R2=0.70, Sres=2.1) and fat mass (FM, R2=0.93, Sres=2.3) than the STM (FFM, R2=0.62, Sres=2.4; FM, R2=0.89,Sres=2.8). There was quite a large variation in the estimates when different BIA prediction equations were used. The equation developed in this study, FFM (kg)=-128.06 + 1.85 x BMI-0.63 x weight + 1.07 x height - 0.03 x resistance +10.0 x waist-hip ratio, yielded a small and unbiased error (0.5 +/- 1.6 kg), with a small residual standard deviation (R2=0.83, Sres=1.6). However, error associated with the estimate of FM was positively related to the degree of FM. BIA(Heitmann) equation yielded unbiased estimates of both FFM and FM (FFM, R2=0.77, Sres=1.8; FM, R2=0.95, Sres=1.9). Both the STM and BIA (manufacturer's equation) resulted in error which was statistically significant and positively correlated with FFM and FM. These results indicate that BIA prediction equations, chosen with care, can improve the performance of equations based upon anthropometric measurements alone in the assessment of body composition in elderly women.

Absorptiometry, Photon↗
PubMed2002

Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects.

BACKGROUND: Betaine (trimethylglycine) is found in several tissues in humans. It is involved in homocysteine metabolism as an alternative methyl donor and is used in the treatment of homocystinuria in humans. In pigs, betaine decreases the amount of adipose tissue. OBJECTIVE: The aim of the study was to examine the effect of betaine supplementation on body weight, body composition, plasma homocysteine concentrations, blood pressure, and serum total and lipoprotein lipids. DESIGN: Forty-two obese, white subjects (14 men, 28 women) treated with a hypoenergetic diet were randomly assigned to a betaine-supplemented group (6 g/d) or a control group given placebo for 12 wk. The intervention period was preceded by a 4-wk run-in period with a euenergetic diet. RESULTS: Body weight, resting energy expenditure, and fat mass decreased significantly in both groups with no significant difference between the groups. Plasma homocysteine concentrations decreased in the betaine group ( +/- SD: 8.76 +/- 1.63 micro mol/L at 4 wk, 7.93 +/- 1.52 micro mol/L at 16 wk; P = 0.030 for the interaction of time and treatment). Diastolic blood pressure decreased without a significant difference between the groups. Serum total and LDL-cholesterol concentrations were higher in the betaine group than in the control group (P < 0.05). CONCLUSION: A hypoenergetic diet with betaine supplementation (6 g daily for 12 wk) decreased the plasma homocysteine concentration but did not affect body composition more than a hypoenergetic diet without betaine supplementation did.

Adult↗
PubMed2002

Combined COMT and GST genotypes and hormone replacement therapy associated breast cancer risk.

Our previous studies suggested that both COMT and GST genotypes might modify individual breast cancer risk. Here, we extended the studies to examine the potential combined effect of these genotypes in susceptibility to breast cancer. Our study population consisted of 483 Finnish breast cancer cases and 482 population control subjects. The odds ratios (ORs) and (95%) confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected confounding factors. No significant increase in the overall breast cancer risk was seen for any combinations of the studied genotypes. However, a substantially increased risk of breast cancer was seen for women who had used hormone replacement therapy (HRT) and simultaneously carried the COMT-L allele containing genotypes and either the GSTP1 Ile/Ile genotype (OR 4.10, 95% CI 1.24-13.6) or the GSTT1 null genotype (OR 4.19, 95% CI 1.30-13.5). These associations appeared to be mainly attributable to long-term users of HRT; the respective ORs were 7.00 (95% CI 1.21-40.6) and 8.36 (95% CI 1.44-49.0) among the users of HRT of more than 30 months. In addition, the combination of COMT-L allele containing genotypes with the GSTM1 null genotype posed a remarkably increased risk (OR 9.10, 95% CI 1.84-45.0) of breast cancer in this study group. These results suggest that the use of HRT could substantially increase the risk of breast cancer among women with specific combinations of the at-risk genotypes of COMT and GST genes.

Adult↗
PubMed2002

The effects of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene on insulin sensitivity and insulin metabolism interact with size at birth.

Type 2 diabetes is known to be associated with a small body size at birth. Body size at birth is an indicator of the intrauterine environment. There is also a well-established association between the peroxisome proliferator-activated receptor (PPAR)-gamma2 gene and type 2 diabetes. We therefore assessed whether the effects of the Pro12Ala polymorphism of the PPAR-gamma2 gene on insulin sensitivity and insulin concentrations in adult life are modified by size at birth. We found that the effects of the Pro12Pro and Pro12Ala polymorphisms of the PPAR-gamma2 gene in elderly people depended on their body size at birth. The well-known association between small body size at birth and insulin resistance was seen only in individuals with the high-risk Pro12Pro allele. In those who had low birth weight, the Pro12Pro polymorphism of the PPAR-gamma2 gene was associated with increased insulin resistance (P < 0.002) and elevated insulin concentrations (P < 0.003). These interactions between the effects of the Pro12Ala polymorphisms of the PPAR-gamma2 gene on adult traits and the effects of birth weight link two previously unknown associations together within the context of type 2 diabetes. We suggest that these findings reflect gene-environment interaction.

Alanine↗