[Drug therapy of hyperglycemia and the prognosis of adult-onset diabetes mellitus].
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Biomedical subjects
Publications and source records attributed to M Uusitupa.
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No studies are available that have compared early defects in glucose metabolism in the offspring of insulin-deficient and insulin-resistant probands with non-insulin-dependent diabetes mellitus (NIDDM). To investigate this issue, we evaluated insulin secretion capacity with oral and intravenous glucose tolerance tests and with the hyperglycemic clamp, and insulin action with the euglycemic insulin clamp in 20 offspring of NIDDM patients with low fasting C-peptide (+/-450 pmol/liter), reflecting deficient insulin secretion (IS-group), 18 offspring of NIDDM patients with high fasting C-peptide (>/= 880 pmol/liter), reflecting insulin resistance (IR-group), and 14 healthy control subjects without a family history of NIDDM. The frequency of impaired glucose tolerance was 45.0% in the IS-group and 50% in the IR-group. The IS-group had lower insulin-glucose response at 30 min in the oral glucose tolerance test (85.2+/-10.0 pmol insulin per mmol glucose) than the control group (136.4+/-23.1 pmol insulin per mmol glucose; P < 0.05) and the IR-group (115.6+/-11.8 pmol insulin per mmol glucose; P = 0.05). Furthermore, the acute insulin response during the first 10 min of an intravenous glucose tolerance test was lower in the IS-group than in the IR-group. Maximal insulin secretion capacity evaluated by C-peptide levels during the hyperglycemic clamp did not differ between the groups. The IR-group had lower rates of whole body glucose uptake (60.1+/-4.6 micromol per lean body mass per minute) than did the control group (84.2+/-5.0 micromol per lean body mass per minute; P < 0.001) or the IS-group (82.6+/-5.9 micromol per lean body mass per minute; P < 0.01) and this was due to reduced glucose nonoxidation. To conclude, both impaired insulin secretion and insulin action seem to be inherited and could represent the primary defects in glucose metabolism in the offspring of NIDDM probands.
The polymorphisms in the uncoupling protein 1 (UCP1, A to G) and beta3-adrenergic receptor (beta3-AR, Trp64Arg) genes have been suggested to be associated with an increased tendency to gain weight. We investigated the frequency of the A to G polymorphism of the UCP1 gene and its effect on basal metabolic rate (BMR) among obese Finns. We also examined the effects of the simultaneous occurrence of the polymorphisms in the UCP1 and beta3-AR genes on BMR. Altogether 170 obese subjects (29 men, 141 women, BMI 34.7beta3.8 kg/m2, age 43+/-8 years, mean+/-SD) participated in the study. The A to G substitution of the UCP1 gene was verified by digestion of the PCR product with Bcl I. The frequency of the A to G polymorphism of the UCP1 gene in obese subjects did not differ significantly from the population-based control subjects (5 vs 1 % for homozygotes (GG) and 35 vs 42 % for heterozygotes (AG), p=0.077, for trend). BMR adjusted for lean body mass, age and sex (adjBMR) was similar among the three UCP1 gene genotypes of obese subjects (AA n=90, AG n=72 or GG n=8). However, the subjects with the polymorphisms in both UCP1 and beta3-AR genes (n=18) had a 79 kcal/day (95% CI 30-128) lower adjBMR than the subjects without these polymorphisms (n=76) (1551+/-77 vs 1629+/-141 kcal/day, p=0.002). Furthermore, adjBMR was 63 kcal/day (95 % CI 7-118 kcal/day) lower in the subjects with both polymorphisms (n=18) compared with the subjects (n=14) who had only the polymorphism in the beta3-AR gene (1551+/-77 vs 1613+/-76 kcal/day, p=0.028). The A to G polymorphism of the UCP1 gene did not have an independent effect on BMR, but its simultaneous existence with the Trp64Arg polymorphism of the beta3-AR gene resulted in more lowered BMR than the Trp64Arg polymorphism of beta3-AR gene alone.
OBJECTIVE: The purpose of this study was to investigate the prevalence and risk factors of dental caries in patients with non-insulin-dependent diabetes mellitus and to determine whether these factors are associated with metabolic control and vascular complications of the disease. STUDY DESIGN: Both the occurrence of caries, acidogenic oral bacteria, and yeasts and salivary flow were studied in 25 patients with non-insulin-dependent diabetes mellitus whose diagnosis had been set 13 to 14 years earlier and in whom the metabolic evolution of the disease was well established. The patients' glycemic control was determined by means of analysis of the blood hemoglobin A1C concentration at the time of dental examination. The control group consisted of 40 nondiabetic subjects in the same age group. Decayed, missing, and filled teeth indices and numbers of surfaces with caries, filled surfaces, and root caries were determined by means of clinical dental caries examination. Stimulated salivary flow was measured, and levels of Streptococcus mutans, lactobacilli, and yeasts were analyzed. RESULTS: The median hemoglobin A1C concentration of the patients was 8.6%, which indicates poor metabolic control of diabetes. No association was found between the metabolic control of disease and dental caries. The occurrence of dental caries was not increased in the patients with non-insulin-dependent diabetes mellitus in comparison with the control subjects. The counts of acidogenic microbes and yeasts did not differ statistically significantly between the groups. There was no association of caries with the prevalence of coronary artery disease or hypertension in either the patients or the control subjects. In a stepwise logistic regression model, a salivary flow of at least 0.8 ml/min was related to the occurrence of dental caries in patients with non-insulin-dependent diabetes mellitus, whereas negligence with respect to dental care was the most important risk predictor in the control group. CONCLUSION: Our results showed no effect of diabetes on the prevalence of caries. However, the caries-protective effect of saliva was partly lost in patients with non-insulin-dependent diabetes mellitus.
OBJECTIVE: The purpose of this investigation was to study the flow rate and organic constituents of whole saliva in relation to autonomic nervous function in patients with non-insulin-dependent diabetes. STUDY DESIGN: We studied the associations of saliva factors and autonomic nervous function in 45 patients with non-insulin-dependent diabetes (mean age, 68 +/- 6 years) and 77 control subjects (mean age, 67 +/- 5 years). The metabolic evolution was well known over a 10-year period from the time of diagnosis. Resting and paraffin-wax-stimulated whole saliva samples were collected and analyzed. Autonomic nervous function was evaluated by measuring heart rate variation during deep breathing and change in systolic blood pressure during orthostatic testing and by means of power spectral analysis of heart rate variability while standing. The effect of drugs used on saliva was also studied. RESULTS: No difference was seen in flow rate between the patients with diabetes and the control subjects; resting flow rates were 0.3 +/- 0.3 ml/min in the patients with diabetes and 0.3 +/- 0.2 ml/min in the control subjects, and stimulated flow rates were 1.2 +/- 1.4 ml/min in the patients with diabetes and 1.2 +/- 0.8 ml/min in the control subjects. The number of drugs used daily correlated with salivary flow rates of the control subjects (p < 0.001) but not with flow rates of the patients with diabetes. The effect of xerogenic medication on salivary flow rates was stronger in patients with diabetes than in control subjects, however. There were no statistically significant differences between patients with diabetes and control subjects in the organic constituents of saliva. The stimulated saliva secretion was associated with total power (rs = 0.343; p = 0.035), medium-frequency power (rs = 0.375; p = 0.020), and high-frequency power (rs = 0.414; p = 0.010) of heart rate variability in patients with diabetes. CONCLUSION: Saliva secretion might be more affected by xerogenic drugs and autonomic nervous dysfunction in patients with non-insulin-dependent diabetes than in nondiabetic control subjects.
The aim of this study was to examine the effect of a very low-calorie diet (VLCD)-induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 +/- 20 kg, age 52 +/- 9 years, range 39-67 years) with OSAS were studied prospectively. They were advised to follow a 2.51-3.35 MJ (600-800 kcal) diet daily for a 3-month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24-h electrocardiograph (ECG) recording. In addition, 15 age-matched, normal-weight subjects were studied. They underwent the Valsalva test, the deep-breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 +/- 20 kg to 105 +/- 21 kg, P < 0.001), the weight loss being 9.2 +/- 4.0 kg (range 2.3-19.5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 +/- 20-19 +/- 18, P < 0.001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 +/- 18 vs. 134 +/- 20, P < 0.05, for systolic blood pressure, 98 +/- 10 vs. 85 +/- 13, P < 0.05, for diastolic blood pressure) and heart rate (67 +/- 10 beats min-1 vs. 60 +/- 13, P < 0.05) at rest than the control group. They had also lower baroreflex sensitivity (4.7 +/- 2.8 ms mmHg-1 vs. 10.8 +/- 7.1 ms mmHg-1, P < 0.01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.
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BACKGROUND: The magnitude of the influence of the apolipoprotein (apo) E genotype on the lipid response to different cholesterol-lowering diet modifications has been controversial. OBJECTIVE: The aim of the study was to investigate the effect of apo E genotype on serum lipid response to the separate modification of dietary fat and cholesterol. DESIGN: A prospective study design with the 3 main apo E genotype groups (3/3, 3/4, and 4/4; n = 15 in each group) was used. Groups were matched for sex, age, body mass index, menopausal status, and baseline serum cholesterol concentration. Subjects followed 3 different diets in fixed order: 1) a standardized baseline diet (38% fat, 300 mg cholesterol/d), 2) a modified National Cholesterol Education Program (NCEP) diet (34% fat, 265 mg cholesterol/d), and 3) the modified NCEP diet + cholesterol (566 mg cholesterol/d). Subjects were middle-aged (50.9 +/- 8.0 y) and mildly hypercholesterolemic (6.55 +/- 1.05 mmol/L). RESULTS: The genotype groups differed in their total cholesterol response to the NCEP diet; the mean (95% CI) decrease being greatest, -14.1% (-19.8%, -8.6% ), in subjects with apo E genotype 4/4 (P = 0.03, analysis of variance). The increase in total cholesterol after addition of 300 mg cholesterol was also greatest in subjects with apo E 4/4 [10.4% (5.8%, 15.1%)] (P = 0.03, analysis of variance). CONCLUSIONS: Apo E genotype modified the lipid response to changes in both dietary fat and cholesterol in mildly hypercholesterolemic subjects; the response was greatest in subjects with apo E genotype 4/4 and even a moderate increase in dietary cholesterol resulted in a 10% elevation in serum total cholesterol in them.
PURPOSE: The aim of this study was to determine the nutritional status of Finnish elite male ski jumpers (N = 21) and age-matched controls (N = 20). METHODS: Nutritional status was assessed by estimating body composition with dual-energy x-ray absorptiometry (DXA), dietary intake with 4-d food records, and assessment of nutritional status was complemented with biochemical and hematological indices. RESULTS: Mean (SD) age (19.7 (3.6) vs 19.8 (3.9) yr, P = 0.675) and stature (176.4 (6.0) vs 178.5 (5.5) cm, P = 0.259) were similar in ski jumpers and in controls, respectively. However, ski jumpers had a lower mean (SD) body weight (61.9 (4.8) vs 71.5 (9.0) kg, P < 0.001) and body fat percentage (8.6 (1.9) vs 16.1 (7.2)%, P < 0.001) than controls. The amount of bone-free lean soft tissue and bone mineral content (BMC) did not differ between the groups, but age- and bone-free lean soft tissue-adjusted bone mineral density (BMD) in lumbar spine (L2-4) and in proximal femur was greater in ski jumpers. Mean (SD) energy intake was lower in ski jumpers than in controls (7.4 (3.3) vs 11.0 (2.6) MJ, P = 0.001), respectively, whereas the percentage of energy derived from carbohydrates was higher in athletes. Despite the markedly lower energy consumption, intake of thiamin, riboflavin, folate, vitamin C, calcium, and iron was similar in both groups, whereas intake of vitamins D and E, magnesium, and zinc was lower in ski jumpers than in controls (P-values range from 0.012 to 0.004). Biochemical and hematological indices showed no abnormalities in either group. CONCLUSIONS: These data suggest that despite the lower body weight and energy intake, nutritional status of the elite Finnish ski jumpers was not compromised as compared with that of nonathletic controls.
Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to affect the affinity of intestinal FABP for fatty acids. This could cause changes in postprandial triglyceride metabolism. In the present study, postprandial lipemia was studied in normotriglyceridemic subjects with genetic variation in the FABP2 gene. Oral fat-loading tests were performed in 8 subjects homozygous for the Thr-encoding allele at codon 54 of the FABP2 gene and in 7 subjects homozygous for the Ala-encoding allele (wild type). There were no significant differences between these 2 groups in age, body mass index, fasting plasma triglyceride and cholesterol levels, or fasting glucose and insulin levels. The increase of plasma triglyceride concentration after the fat test meal was significantly greater in subjects who were homozygous for the Thr-54 allele (area under the response curve, 4.27+/-1.31 versus 2.49+/-1.18 mmol/L x h-1, P=0.04). The difference was seen in both chylomicron (2.51+/-0. 98 versus 1.41+/-0.74 mmol/L x h-1, P=0.03) and very low-density lipoprotein triglycerides (1.57+/-0.77 versus 0.99+/-0.40 mmol/L x h-1, P=0.04). Postprandial triglyceride response correlated with fasting triglycerides in the Ala-54 homozygotes (r=0.79, P=0.05) but not in the Thr-54 homozygotes (r=0.09), who showed a strong correlation between triglyceride and insulin responses (r=0.83, P=0. 02). With reservations related to a small number of subjects studied, these results indicate that the Thr-encoding allele of the FABP2 gene is associated with increased postprandial lipemia. The lipemic response was associated with postprandial insulin response, suggesting that in the Thr-54 homozygotes, altered postprandial lipemia may also modify insulin action or vice versa.
This study examined whether the Trp64Arg mutation in the beta3-adrenergic receptor (beta3AR) and the A-->G mutation in the uncoupling protein-1 (UCP-1) genes have associations with weight loss and subsequent weight maintenance. Seventy-seven obese (body mass index range, 29-46 kg/m2), clinically healthy, premenopausal women were studied. A 12-wk weight reduction by very low calorie diet (VLCD) was followed by a 40-wk weight maintenance phase. The subjects were divided into four groups according to their beta3AR and UCP-1 genotype: no mutation (control; n=37), only Trp64Arg mutation in the beta3AR gene (n=12), only A-->G mutation in the UCP-1 gene (n=23), and both mutations (n=5). Subjects with both mutations had a lower weight reduction during VLCD than the controls [-10.5+/-0.6 (+/-SEM) vs. -14.0+/-0.5 kg; P=0.051, by ANOVA]. During the maintenance phase, weight in subjects with both mutations increased by 5.8+/-1.5 kg, but remained unchanged in the controls (-0.5+/-0.8 kg; P=0.041). The changes in weight in subjects with only one of the mutation were close to the results in the controls. Resting energy expenditure, adjusted for fat mass, fat-free mass, and maximal aerobic power, did not change differently between the groups throughout the study. The results suggest that a combination of the Trp64Arg mutation in the beta3AR and the A-->G mutation in the UCP-1 genes may be associated with faster weight gain after a VLCD.
OBJECTIVE: To investigate whether there are differences in serum leptin levels between the offspring of non-insulin-dependent diabetes mellitus (NIDDM) patients representing different phenotypes of NIDDM, and furthermore to investigate the role of different fat tissue (subcutaneous fat area (SCFAT) and intra-abdominal fat area (IAFAT)) and insulin sensitivity on serum leptin levels. DESIGN: Twenty non-diabetic offspring of NIDDM patients with insulin secretion deficient phenotype (IS-group), 18 non-diabetic offspring of NIDDM patients with insulin resistant phenotype (IR-group) and 14 healthy control subjects without a family history of diabetes were studied. METHODS: Serum leptin levels were measured by RIA. SCFAT and IAFAT were measured by computed tomography. the total fat mass (TFM) by bioelectrical impedance and the whole body glucose uptake (WBGU) by the euglycemic hyperinsulinemic clamp technique. RESULTS: Subjects of the control group (P = 0.003) and the IS-group (P<0.001) had lower serum leptin levels than subjects of the IR-group even after adjustment for gender (P<0.001). TFM (P = 0.009), fasting plasma insulin (P = 0.003) and for IAFAT (P<0.001). The differences weakened after adjustments for SCFAT (P = 0.028) or WBGU (P = 0.040) and disappeared after adjustment for both SCFAT and WBGU (P = 0.058). In the stepwise multiple regression analyses SCFAT. WBGU and gender explained 58% of the variation of serum leptin levels whereas IAFAT failed to be a significant determinant of serum leptin levels. CONCLUSIONS: The higher serum leptin levels in the IR-group was markedly, but not solely, explained by lower rates of WBGU and higher SCFAT. SCFAT was shown to be a more important determinant of serum leptin levels than IAFAT among these study groups.
The periodontal status of 25 patients with non-insulin dependent diabetes mellitus (NIDDM) (age range 58 to 76) was investigated and compared with 40 non-diabetic control subjects (age range 59 to 77). Surfaces with visible plaque and bleeding after probing, calculus, recessions, and pathological pockets were examined. The total attachment loss was calculated as a sum of recessions and pockets in millimeters. Mesial and distal bone loss was measured from panoramic radiographs and mean alveolar bone loss was calculated. Periodontal disease was considered advanced when mean alveolar bone loss was over 50%, or 2 or more teeth had pockets > or = 6 mm. Microbiological analysis comprised the detection of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus by a polymerase chain reaction (PCR) method. Patients with NIDDM had significantly more often advanced periodontitis than control subjects, 40.0% and 12.5%, respectively. Diabetic patients did not harbor more pathogens than the control subjects. The HbA1C level deteriorated in patients with advanced periodontitis, but not in other patients with NIDDM, when compared to the situation 2 to 3 years earlier. Advanced periodontitis seems to be associated with the impairment of the metabolic control in patients with NIDDM, and a regular periodontal surveillance is therefore necessary.
We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age +/- SEM: 65.5 +/- 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age +/- 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/3, E3/3 vs E3/4, E4/4) to the incidence of clinical macrovascular disease and its risk factors and the incidence of microvascular complications of diabetes during the first 10 years of NIDDM, as well as carotid intima-media thickness measured by B-mode ultrasound at the 10-year examination. In patients with NIDDM, apo E4 genotype showed no relationship to clinical events or carotid intima-media thickness. However, in the control subjects with apo E4, the incidence of non-fatal myocardial infarction during the follow-up was increased (apo E4 positivity: 17.1%; apo E4 negativity 5.1%; p = 0.035) and they had higher common carotid intima-media thickness than those with apo E2/3 or apo E3/3 (1.15 +/- 0.05 mm vs 1.01 +/- 0.03 mm, p = 0.008). Apo E genotype groups showed no relationship to microvascular complications of diabetes, although control subjects with apo E4 positivity showed a higher frequency of microalbuminuria than those lacking apo E4. We conclude that apo E4 was a marker of vascular disease and increased atherosclerosis in non-diabetic subjects, whereas in the diabetic patients these relationships were absent. It is likely that NIDDM per se influences the vascular risk so overwhelmingly that the effects of other risk factors are obscured.
OBJECTIVE: To investigate the determinants of resting energy expenditure (REE) in obese non-diabetic Caucasian women. DESIGN: A cross-sectional survey study before the beginning of a weight-reduction program. SUBJECTS: 141 obese, non-diabetic women of Caucasian origin (BMI 34.8 +/- 3.7 kg/m2, age 43.2 +/- 8.0 y, mean +/- s.d.). MEASUREMENTS: Resting energy expenditure (an indirect calorimetry), body composition (a bioelectrical impedance), fat distribution (anthropometry) and heart rate (ECG) were determined after 12 h overnight fast and apolipoprotein E phenotype was examined. RESULTS: In a linear multiple regression analysis fat-free mass, fat mass and age together with heart rate and waist-hip ratio emerged as significant determinants of REE. In the other regression model, also serum insulin emerged as a significant determinant of REE, in addition to fat-free mass, fat mass and age. There was no significant differences in REE among the different apolipoprotein E phenotype groups. CONCLUSION: Besides fat-free mass, also fat mass, age, heart rate, waist-hip-ratio, and serum insulin level make a significant contribution to REE in obese women.
OBJECTIVES: To investigate how abdominal adiposity assessed by different anthropometric measurements and dual-energy X-ray absorptiometry measurements is associated with metabolic risk factors for cardiovascular disease and non-insulin-dependent diabetes mellitus in obese women. DESIGN: Cross-sectional study. SUBJECTS: Forty-three healthy, obese, middle-aged women (age: 29-64 y, BMI: 28-42 kg/m2). MEASUREMENTS: (1) Anthropometry: waist circumference, waist-to-hip ratio, waist-to-height ratio, abdominal sagittal and transverse diameters and their ratio. (2) Dual-energy X-ray absorptiometry: the amount of total and regional abdominal fat. (3) Metabolic measurements: serum total, VLDL, LDL, HDL cholesterol, triglycerides, fasting and postglucose serum insulin and glucose. RESULTS: After adjustment for age and BMI, all the anthropometric measurements except waist-to-hip ratio and waist-to-height ratio related significantly to HDL and LDL cholesterol. On the other hand, waist-to-hip ratio and waist-to-height ratio showed an association with triglycerides. In addition, all the anthropometric measurements except transverse diameter correlated significantly with fasting insulin and fasting glucose. Waist-to-hip ratio was the only measure that associated with 2 h glucose concentration. The differences between the correlation coefficients were not statistically significant in the z-transformed correlation coefficient test. As to dual-energy X-ray absorptiometry results, the region from the dome of diaphragm to the top of femur ('abdominal fat') and the area between the first and the fourth lumbal vertebrae ('upper lumbal fat') inversely related to HDL cholesterol and positively to triglycerides. Both of these regions correlated significantly with fasting insulin, and "upper lumbal fat' associated also with fasting glucose even after adjustment for age and BMI. CONCLUSION: None of the anthropometric measurements (waist circumference, waist-to-hip ratio, waist-to-height ratio or sagittal diameter) was significantly superior to others to assess the metabolic risk profile. 'Upper lumbal fat' (the area between the first and the fourth lumbal vertebrae) measured by dual-energy X-ray absorptiometry discerned obese women with elevated fasting insulin and fasting glucose.
1. Leptin is generally thought to play a key role in the regulation of eating. However, its real role in human eating behaviour is still poorly known. Therefore, the role of leptin in the regulation of eating was examined in obese binge- and non-binge-eating women during exposure to food and food-related stimuli. 2. Eleven binge- and ten non-binge-eating obese women took part in the study. In addition to serum leptin, serum insulin, non-esterified fatty acids, plasma glucose, salivation, the feeling of hunger and the desire to eat were repeatedly measured during the experiment. 3. Serum leptin levels did not differ between the binge- and non-binge-eating women. Neither were leptin levels associated with the feeling of hunger or the desire to eat food, nor with the amount or composition of food eaten. During food exposure leptin levels did not change, whereas at the same time serum insulin levels increased and serum non-esterified fatty acid levels decreased. The change in salivation during food exposure was inversely associated with the fasting leptin level. 4. This study indicates that serum leptin does not play a role in the regulation of eating in obese women, at least not in the short term. Furthermore, leptin levels are not different in obese binge-eating women as compared with obese non-binge-eating women. Interestingly, high fasting leptin levels may be associated with a decreased salivation response in the presence of food and food-related stimuli.
Impaired antioxidant defences may predispose to the increased resting and exercise-induced oxidative stress found in patients with insulin-dependent diabetes mellitus (IDDM). We investigated major erythrocyte antioxidant enzyme activities at rest and in response to sustained, moderate intensity physical exercise in young diabetic men (n = 9) previously reported to have markedly elevated plasma lipid peroxidation and blood glutathione levels compared with control men (n = 13) (Laaksonen et al. 1996). At rest, erythrocyte glutathione reductase activity was 15% higher in the diabetic group (P = 0.049). Se-glutathione peroxidase and glutathione-S-transferase activities were similar in both groups. Red cell Cu, Zn-superoxide dismutase and catalase activities were lower in the IDDM group (P = 0.033 and P = 0.023, respectively). After 40 min of exercise at 60% of the subjects' peak oxygen consumption, Se-glutathione peroxidase activity rose by about 14% in the control group (P = 0.003), but not in the IDDM group (P = 0.47). Exercise did not cause significant changes in other enzyme activities in either group. To conclude, lower erythrocyte Cu, Zn-superoxide dismutase and catalase activity in young men with IDDM at rest may contribute to increased oxidative stress. On the other hand, increased glutathione reductase activity may represent a compensatory upregulation of glutathione homeostasis in response to increased oxidative stress. Upregulation of Se-glutathione peroxidase activity in response to physical activity appeared to be impaired in men with IDDM.