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Biomedical subjects

M Uusitupa

Publications and source records attributed to M Uusitupa.

At least 91 records · Page 5Linked to original sources

Changes in autonomic nervous function during the 4-year follow-up in middle-aged diabetic and nondiabetic subjects initially free of coronary heart disease.

OBJECTIVES: To study the changes in autonomic nervous function during the 4-year follow-up period in diabetic patients and to investigate factors predicting autonomic nervous dysfunction. DESIGN: A 4-year follow-up study. SETTING: At baseline the study subjects without known cardiovascular disease were recruited from a large group of diabetic and nondiabetic subjects selected randomly from a baseline population. SUBJECTS: Middle-aged control subjects (n = 44), patients with insulin-dependent diabetes mellitus (n = 32) and patients with non-insulin-dependent diabetes mellitus (n = 32) were studied at baseline and after the 4-year follow-up. INTERVENTIONS: Autonomic nervous function tests and exercise test at baseline and after the 4-year follow-up. RESULTS: At the baseline, heart rate variation during deep breathing was significantly lower in patients with insulin-dependent diabetes (13.0 +/- 1.2 beats min-1; P < 0.05) and in patients with non-insulin-dependent diabetes (12.9 +/- 1.5 beats min-1; P < 0.05) than in control subjects (16.6 +/- 1.1 beats min-1). At baseline, autonomic nervous function score was significantly higher indicating disturbed autonomic nervous function in patients with insulin-dependent diabetes (1.74 +/- 0.19; P < 0.01) than in control subjects (1.24 +/- 0.14), but the difference was not significant between control subjects and patients with non-insulin-dependent diabetes (1.47 +/- 0.12). During the follow-up, autonomic nervous function score increased in patients with non-insulin-dependent diabetes to 2.00 +/- 0.21 (P < 0.001, as compared to baseline), but did not change in patients with insulin-dependent diabetes (1.77 +/- 0.18) or control subjects (1.22 +/- 0.12). In both diabetic groups, the deterioration of autonomic nervous function score during the 4-year follow-up was associated with poor glycaemic control at baseline. Clinical manifestation of coronary heart disease was found in three (7%) control subjects, 12 (37%; P < 0.001) patients with insulin-dependent diabetes and 11 (34%; P < 0.01) patients with non-insulin-dependent diabetes mellitus at follow-up examination. Autonomic nervous function was more abnormal in those insulin-dependent diabetic patients with coronary heart disease than those without. CONCLUSIONS: During the 4-year follow-up the impairment in autonomic nervous function occurred mainly in patients with noninsulin-dependent diabetes. Poor glycaemic control appears to be an important determinant of the progression of autonomic nervous dysfunction in diabetes.

Aged↗

Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects.

Fatty acid binding protein 2 gene (FABP2) has been proposed to be an important candidate gene for insulin resistance; therefore, it also could be a promising candidate gene for obesity. We screened the whole coding region of the FABP2 gene in 40 obese nondiabetic Finnish subjects. Furthermore, we investigated the effects of the codon 54 polymorphism of this gene (Ala-->Thr) on insulin levels and basal metabolic rate in 170 obese subjects. The frequencies of the variants found in exon 4 (GTA-->GTG) and 3'-noncoding region (GCGCA-->GCACA), as well as the allele frequencies for the variable lengths of the ATT repeat sequence in intron 2 did not differ between the obese subjects and nonobese controls. The frequency of threonine-encoding allele in codon 54 of the FABP2 gene did not differ between obese and control subjects (28 vs. 29%, respectively). In the obese group there were no differences in gender distribution, age, weight, body mass index, lean body mass, percentage of body fat, waist circumference, and waist-to-hip ratio among the individuals homozygous for Ala54, heterozygous for Thr54, and homozygous for Thr54-encoding alleles. Similarly, fasting serum insulin, glucose, lipids and lipoprotein concentrations, basal metabolic rate (adjusted for lean body mass and age), respiratory quotient, and rates of glucose and lipid oxidation did not differ among the groups. We conclude that obesity is not associated with specific variants in the FABP2 gene. Furthermore, the codon 54 Ala to Thr polymorphism of this gene does not influence insulin levels or basal metabolic rate in obese Finns.

Adult↗

Polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns.

Low basal metabolic rate (BMR) is a risk factor for weight gain and obesity. The polymorphism at codon 64 of the beta3-adrenergic receptor gene has been suggested to be associated with BMR. We investigated the frequency of the Trp64Arg of the beta3-adrenergic receptor gene and the effects of this polymorphism on BMR in obese Finns. Altogether, 170 obese subjects (29 men, 141 women, BMI 34.7 +/- 3.8 kg/m2, mean +/- SD) participated in the study. The frequency of the Trp64Arg polymorphism was 19%. None of the obese subjects were homozygous for the Arg-encoding allele. The frequency of the Trp64Arg polymorphism in obese Finns did not differ from nonobese and normoglycemic control subjects. BMR adjusted for lean body mass and age was lower in subjects with the Trp64Arg polymorphism (n = 20) than in normal homozygotes Trp64Trp (n = 99) (1,569 +/- 73 vs. 1,635 +/- 142 kcal/day, P = 0.004). For the female group (n = 98), the respective values were 1,501 +/- 66 kcal/day vs. 1,568 +/- 127 kcal/day (P = 0.004). There were no significant differences in weight, BMI, waist-to-hip ratio, lean body mass, percentage of fat, and respiratory quotient between the groups with or without the Trp64Arg polymorphism. Neither serum glucose nor insulin levels differed between the two groups. We conclude that the Trp64Arg polymorphism of the beta3-adrenergic receptor gene affects basal metabolic rate in obese Finns but does not have significant effect on glucose metabolism.

Adult↗

[Diabetic nephropathy--screening, follow-up and treatment. Nephropathy Study Groups of The Finnish Diabetes Organization].

Owing to advances in the diagnosis and treatment of diabetic nephropathy, its management has become more active and is now initiated earlier after the presence of microalbuminuria has been established. In 1996 the Finnish Diabetic Association's nephropathy group issued recommendations concerning screening for diabetic nephropathy, and treatment and follow-up of patients with the disease.

Adolescent↗

Body-size indicators and risk of breast cancer according to menopause and estrogen-receptor status.

Associations between the risk of breast cancer and body-size indicators at the time of breast-cancer diagnosis were assessed among 328 pre-menopausal or post-menopausal cases and 417 controls participating in the Kuopio Breast Cancer Study. This case-control study follows the protocol of the international Collaborative Study of Breast and Colorectal Cancer. When the potential confounding factors were taken into account, tallness was related to increased risk of breast cancer, especially in post-menopausal women, whereas no clear association with body-mass index (BMI) was found. Waist-to-hip ratio (WHR) was the most important risk factor in both pre-menopausal and post-menopausal women. The post-menopausal cases with high positive estrogen-receptor status (ER++) had the highest weight and BMI; they had also the biggest weight gain since the age of 20. However, the association between WHR and breast cancer appeared to be independent of estrogen-receptor status. Our results suggest that WHR may be a better marker for breast cancer than the degree of adiposity.

Adult↗

Vitamin E concentration in breast adipose tissue of breast cancer patients (Kuopio, Finland).

Previous data on animals and humans suggest that vitamin E may be a protective factor against cancer. A low dietary vitamin E intake has been suggested to increase the risk of breast cancer. We examined the dietary intake and the concentration of vitamin E in breast adipose tissue of women in Kuopio, Finland, diagnosed between 1990 and 1992 with benign breast disease (n = 34) and with breast cancer (n = 32). In postmenopausal women, lower dietary intake (P = 0.006) and a smaller concentration of vitamin E in breast adipose tissue (P = 0.024) were observed in breast cancer patients than in subjects with benign breast disease. Partial correlation showed that the vitamin E concentration in the breast adipose tissue correlated positively with the dietary intake of vitamin E (r = 0.25, P = 0.023), indicating that the vitamin E concentration in breast adipose tissue reflects the dietary intake of vitamin E.

Adipose Tissue↗

Measurement of myocardial accumulation of 123I-metaiodobenzylguanidine for studying cardiac autonomic neuropathy in diabetes mellitus.

The association of myocardial 123I-metaiodobenzylguanidine (MIBG) accumulation and autonomic neuropathy, as well as factors known to affect autonomic nervous function, were studied in a group of 12 diabetic patients representing different degrees of autonomic failure. The early myocardial uptake phase of 123I-MIBG was measured by calculating the peak net influx rate for the first 30 min after the 123I-MIBG injection and by single photon emission computed tomography (SPECT) imaging 1 h after the injection. The retainment of 123I-MIBG in the myocardium was measured using SPECT imaging 6 h after the injection, and myocardial uptake and the myocardium/liver uptake ratio were calculated. The 6-h myocardium/liver uptake ratio of 123I-MIBG was significantly (p < 0.05) lower in the diabetic patients with clinically evident autonomic neuropathy compared with those without autonomic neuropathy. Greater body mass index was associated with lower peak net influx rate and 1-h myocardial uptake of 123I-MIBG, and greater diastolic blood pressure was associated with lower 1-h myocardial uptake of 123I-MIBG, whether or not the patients had diabetic autonomic neuropathy. In conclusion, reduction in the 6-h myocardium/liver uptake ratio of 123I-MIBG is related to diabetic autonomic neuropathy. Because the early 123I-MIBG accumulation in myocardium is reduced in diabetic patients with greater body mass index and diastolic blood pressure, irrespective of autonomic neuropathy, our results encourage the use of the late myocardial accumulation of 123I-MIBG for studying sympathetic neuropathy in the diabetic heart.

3-Iodobenzylguanidine↗

Does lactose intolerance predispose to low bone density? A population-based study of perimenopausal Finnish women.

The relationship of lactase malabsorption to osteoporosis is unclear. We examined the relationship of self-reported lactose intolerance (LI) to bone mineral density (BMD) in perimenopausal Finnish women. A random population sample of 2025 women aged 48-59, who underwent spinal and femoral BMD measurement with dual X-ray absorptiometry in Kuopio, Finland during 1989-1991 formed the study population. Out of these women, 162 women reported LI. The mean dairy calcium intake was 558 mg/day in women with LI and 828 mg/day in other women (p < 0.0001). The mean spinal BMDs were 1.097 and 1.129 g/cm2 (-2.8%) (p = 0.016) and the mean femoral BMDs were 0.906 and 0.932 g/cm2 (-2.8%) (p = 0.012) for the LI and other women, respectively. After adjusting for weight, age, years since menopause, and the history of hormone replacement therapy, these differences changed to -2.7% (p = 0.016) for the spinal and -2.4% (p = 0.012) for the femoral BMD, respectively. Dairy calcium intake was an independent determinant of femoral BMD. The addition of calcium intake variables into the multivariate model did not affect the spinal BMD difference, but weakened the femoral BMD difference to -1.9% (p = 0.075). Our results suggest that LI slightly reduces perimenopausal BMD, possibly through reduced calcium intake.

Bone Density↗

Cardiac sympathovagal balance during sleep apnea episodes.

The main acute cardiovascular effects of obstructive sleep apnea syndrome (OSAS) are elevation of blood pressure and reflectory bradycardia, which are followed by an abrupt tachycardia on resumption of breathing. This haemodynamic instability is related to hypoxemia and arousal, and may lead to increased risk from cardiac arrhythmias and sudden cardiac death, as well as to the development of chronic arterial hypertension, in these patients. The aim of this study was to apply frequency domain analysis of heart rate variability (HRV) measured from continuous electrocardiogram (ECG) recordings to evaluate how cardiac autonomic function, and especially cardiac sympathovagal tone, changes during sleep apnea episodes. We identified 41 apneas leading to more than 4%-unit arterial oxygen desaturation in 12 patients (11 men, 1 woman (correction for women), age range 27-67 years). Frequency domain analysis of HRV was performed from ECG recordings using 4 min epochs starting 20 min before apnea began and lasting 20 min after the beginning of apnea. The mean (+/-SEM) fall in oxygen saturation during the apnea was 6.8 +/- 0.6%-units. While high frequency band (HF, reflects cardiac vagal activity) remained unchanged, low frequency band (LF, mainly sympathetic activity) showed a constant increase, leading to significant change in the sympathovagal balance (LF/HF ratio). In conclusion, concordantly with previous peripheral sympathetic-nerve recordings, frequency domain analysis of HRV is able to detect sympathetic activation during sleep apnea episodes, leading to marked change in the sympathovagal balance.

Adult↗

Carotid artery intima-media thickness in elderly patients with NIDDM and in nondiabetic subjects.

BACKGROUND AND PURPOSE: The risk of atherosclerotic vascular disease is increased both in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in those with impaired glucose tolerance compared with nondiabetic subjects. Although classic cardiovascular risk factors are operative in subjects with NIDDM, other factors closely related to insulin resistance syndrome such as diabetic dyslipidemia and hyperglycemia itself may contribute to an excessive cardiovascular disease risk in subjects with NIDDM. The purpose of this study was to investigate the carotid intimal-medial thicknesses (IMTs) and their determinants in elderly patients with NIDDM and in control subjects. METHODS: We investigated the common carotid and carotid bifurcation IMTs and their determinants in groups of elderly patients (n = 84, age 67.2 +/- 0.6 years) with NIDDM and in 119 control subjects (21 with impaired and 98 with normal glucose tolerance; ages 67.5 +/- 1.0 and 65.1 +/- 0.6 years, respectively). RESULTS: Common carotid and carotid bifurcation IMTs were greater in the NIDDM group than in control subjects (P < .05 to .01). In NIDDM patients, the mean carotid IMT correlated with postglucose 1-hour plasma insulin (r = .305, P = .01, adjusted for age and sex), serum LDL triglyceride (r = .237, P < .05), and apolipoprotein B concentrations (r = .263, P < .05). Fasting plasma immunoreactive insulin, proinsulin, or specific insulin levels were not significantly associated with carotid IMT. Both diabetic status (P < .05) and the presence of clinical macrovascular disease (P < .01) contributed independently to carotid IMT. CONCLUSIONS: Carotid IMT was greater in NIDDM patients than in control subjects. The main determinants of IMT in NIDDM patients were related to both postglucose insulin levels and abnormal lipoprotein profiles characteristic of NIDDM and insulin resistance syndrome. Treatment of these factors is likely to reduce the atherosclerotic burden in NIDDM.

Aged↗

Increased resting and exercise-induced oxidative stress in young IDDM men.

OBJECTIVE: To assess the effect of acute physical exercise on oxidative stress and glutathione redox status and the relation to physical fitness in otherwise healthy young men with IDDM. RESEARCH DESIGN AND METHODS: Nine men with IDDM (HbA1 7.3 +/- 1.7%), ages 21-30 years, and 13 matched control subjects exercised on a bicycle ergometer for 40 min at 60% of their maximal oxygen consumption (VO2max). Oxidative stress was assessed with plasma thiobarbituric acid reactive substance (TBARS) levels (an index of lipid peroxidation) and, in response to exercise, also glutathione redox status. For glutathione redox status, blood total glutathione (TGSH) and oxidized glutathione (GSSG) were determined. Blood samples were drawn immediately before and after exercise. RESULTS: Resting plasma TBARS levels were markedly elevated in diabetic patients (2.2 +/- 0.7 vs. 0.9 +/- 0.4 mumol/l; P = 0.0002). Mean blood TGSH was higher in diabetic subjects (1,203 +/- 221 vs. 936 +/- 156 mmol/l; P = 0.002), with no significant difference in GSSG or GSSG/TGSH values. Exercise increased plasma TBARS and blood GSSG by approximately 50% in both groups. Resting plasma TBARS had a strong inverse correlation (r = -0.82; P = 0.006), and the exercise-induced percentage increase in TBARS had a strong positive correlation (r = 0.81, P = 0.008) with VO2max in diabetic subjects only. CONCLUSIONS: Glutathione redox status appears to be adequate in healthy young moderately active diabetic men. On the other hand, they demonstrated increased resting and postexercise oxidative stress as indicated by plasma TBARS. Although exercise acutely induces oxidative stress, in patients with diabetes, physical fitness may have a protective effect against oxidative stress.

Adult↗

The effects of weight loss on insulin sensitivity, skeletal muscle composition and capillary density in obese non-diabetic subjects.

OBJECTIVE: To investigate whether the improvement in insulin resistance by weight loss is associated with changes in skeletal muscle fiber composition or capillary density. DESIGN: Longitudinal, clinical intervention study of a 2.1 MJ diet daily for 3 weeks and 3.4 MJ diet daily for 9 weeks. SUBJECTS: Seven obese (age: 41-59 y, five men, BMI > 34 kg/m2) non-diabetic subjects. MEASUREMENTS: Insulin action was measured by the euglycaemic hyperinsulinaemic clamp before and after 3 and 12 weeks of the very low calorie diet. In addition, the skeletal muscle biopsies were taken before and after the 12 weeks. RESULTS: During the 12 weeks, the subjects lost about 16% of body weight. The weight loss was accompanied by a nearly two-fold increase in total body glucose disposal rate (GDR; baseline vs 12 weeks: 842 +/- 91 vs 1505 +/- 242 mu mol/m2/min; p < 0.05). Most marked improvement was observed in non-oxidative component of GDR, which increased 2.7-fold as compared to baseline (292 +/- 113 vs 788 +/- 231 mu mol/m2/min; p < 0.05). However, no significant change in proportion of type II fibers as well as in skeletal muscle capillary density occurred during the study. CONCLUSION: In obese non-diabetic subjects the improvement in insulin sensitivity induced by weight loss was not accompanied by marked changes in skeletal muscle fiber composition or capillary density. However, due to small number of subjects studied, the role of structural changes in the muscle fiber composition cannot be entirely ruled out.

Adult↗

Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure.

The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme (ACE) inhibitor (cilazapril) on both office and ambulatory blood pressure (BP) levels in free living subjects with elevated BP. The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly. After exclusions, 39 subjects (24 men, 15 women, aged 28-65 years) with mildly to moderately elevated BP completed the study. After 3 months run-in period with placebo (first month on normal-salt and the next 2 months on sodium-restricted diet) the subjects were randomised into either salt-restriction placebo or salt-restriction cilazapril (2.5 mg daily) groups for 3 months. In the whole group, 24-h urinary sodium excretion decreased (mean +/- s.d.) from 198 +/- 60 to 112 +/- 59 mmol (4 weeks vs 24 weeks, P < 0.001). Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase (-7.1 [95% Cl -11.2; -3.0] and -4.2 [95% Cl -6.6; -1.8] mm Hg for systolic and diastolic BP), and similarly the daytime ambulatory BP (ABP) was reduced during this period (-2.8 [95% Cl -5.2; -0.5] and -2.8 [95% Cl -4.5; -1.2] mm Hg, systolic (SBP) and diastolic blood pressure (DBP) respectively). No changes were observed in the night time ABP. Addition of cilazapril to sodium-restriction enhanced significantly the office BP (-13.2, [95% Cl -20.2; -6.2], and -9.1 [95% Cl -13.5; -4.7]) and daytime ABP (-5.9, [95% Cl -10.1; -1.8] and -5.3, [95% Cl -8.8; -1.9]) reduction. Blood glucose, plasma insulin or serum lipids did not change during the study. Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension. The antihypertensive effect of cilazapril could be enhanced by sodium restriction.

Adult↗