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L Niskanen

Publications and source records attributed to L Niskanen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Blood glutathione homeostasis as a determinant of resting and exercise-induced oxidative stress in young men.

Although the importance of glutathione in protection against oxidative stress is well recognized, the role of physiological levels of glutathione and other endogenous antioxidants in protecting against exercise-induced oxidative stress is less clear. We evaluated the role of glutathione and selected antioxidant enzymes as determinants of lipid peroxidation at rest and in response to exercise in men (n = 13-14) aged 20-30 years, who cycled for 40 min at 60% of their maximal oxygen consumption (VO2max). Levels of plasma thiobarbituric acid reactive substances (plasma TBARS) and blood oxidised glutathione (GSSG) increased by about 50% in response to exercise. Mean blood reduced glutathione (GSH) decreased by 13% with exercise. Of the measured red blood cell (RBC) antioxidant enzyme activities, only selenium-dependent glutathione peroxidase (Se-GPX) activity rose following exercise. In univariate regression analysis, plasma TBARS levels at rest predicted postexercise plasma TBARS and the exercise-induced change in total glutathione (TGSH). Blood GSSG levels at rest were strongly determinant of postexercise levels. Multiple regression analysis showed blood GSH to be a determinant of plasma TBARS at rest. The relative changes in TGSH were determinant of postexercise plasma TBARS. In summary, higher blood GSH and lower plasma TBARS at rest were associated with lower resting, and exercise-induced, lipid peroxidation. Subjects with a favourable blood glutathione redox status at rest maintained a more favourable redox status in response to exercise-induced oxidative stress. Changes in blood GSH and TGSH in response to exercise were closely associated with both resting and exercise-induced plasma lipid peroxidation. These results underscore the critical role of glutathione homeostasis in modulating exercise-induced oxidative stress and, conversely, the effect of oxidative stress at rest on exercise-induced changes in glutathione redox status.

Adult↗
PubMed1999

Non-suppressed thyrotropin and elevated thyroglobulin are independent predictors of recurrence in differentiated thyroid carcinoma.

OBJECTIVE: Although in most cases differentiated thyroid carcinoma (DTC) responds to surgery and radioiodine (RaI) therapy, some patients will have recurrence and eventually cancer-related death. However, although various prognostic factors of DTC have been identified (e.g. staging, suppressed thyrotropin), none of the previous studies have assessed simultaneously their role in multivariate analysis. DESIGN AND METHODS: In this retrospective population-based study, we reviewed the clinicopathological data of 254 DTC patients treated in eastern Finland during the years 1976-1995, for clinical characteristics, primary treatment, follow-up and cancer recurrence. Tumor stage was based on pathological tumor-node-metastasis (pTNM) classification, and histopathological specimens were re-evaluated. RESULTS: DTC recurrence occurred in 33 patients (13%). In univariate analyses, the predictors of recurrence were older age (>60 years, P<0.05), follicular tumor type (P<0.01), pTNM classification system (P<0.05) and post-ablative radioiodine uptake outside the neck (P<0.05). Non-suppressed serum thyrotropin (TSH) and elevated serum thyroglobulin (>3 microg/l) measured one year after operation were both related to tumor recurrence (P<0.05 and P<0.001 respectively). In multivariate analysis the independent predictors for recurrence were both elevated thyroglobulin (P<0.001) and non-suppressed TSH (P<0.05) independent of histology, pTNM stage and RaI uptake. Adjusted risk ratio for recurrence of DTC for unsuppressed thyrotropin was 2.3, for elevated thyroglobulin 14.0 and, if both conditions were present, the risk ratio increased to 45.1. CONCLUSION: Our results suggest that both non-suppressed serum TSH and elevated serum thyroglobulin are related to an increased risk of DTC recurrence independent of tumor type and pTNM stage.

Adenocarcinoma, Follicular↗
PubMed1998

Postmenopausal hormone replacement therapy and autoantibodies against oxidized LDL.

OBJECTIVES: Oxidative modification of low-density lipoprotein (oxLDL) has been suggested to play an important role in the pathogenesis of atherosclerosis, and autoantibodies against oxLDL have recently found to reflect this process. The antioxidant effect and inhibition of LDL oxidation may be one of the cardioprotective mechanisms of postmenopausal estrogen therapy. METHODS: The effects of postmenopausal hormone replacement therapy (HRT) on the concentrations of serum lipids and oxLDL autoantibodies were studied in a population-based prospective 1-year study with 64 early postmenopausal women (mean age 52.2 +/- 0.4 (S.E.M.) years). The participants were randomized into two treatment groups: HRT-group: Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate alone or in combination with vitamin D3, 300 IU/day + calcium lactate, 500 mg/day (n = 31) and the non-HRT-group: Calcium lactate, 500 mg/day alone or in combination with vitamin D3, 300 IU/day (n = 33). The groups were well matched regarding age, body mass index and baseline serum lipid concentrations. RESULTS: The serum concentrations of total cholesterol and LDL-cholesterol decreased in the HRT-group (4.1%, P = 0.05 and 6.4%, P = 0.03, respectively, paired t-test) but did not change in the non-HRT-group. No changes in the serum concentrations of HDL-cholesterol or triglycerides were observed. Additionally, no changes in oxLDL autoantibody concentrations were observed in either group. CONCLUSIONS: Although 1-year HRT lowered serum total- and LDL-cholesterol levels, it did not influence oxLDL antibody titers. On the basis of the present results we cannot question the possibility of there being beneficial effects of HRT on the oxidative modification of LDL. However, this effect is not reflected in the levels of oxLDL autoantibodies.

Autoantibodies↗
PubMed1998

Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands.

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.

Adipose Tissue↗
PubMed1998

Effects of postmenopausal hormone replacement therapy with and without vitamin D3 on circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D3 on vitamin D metabolites (25OHD and 1,25(OH)2D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D3 group (vitamin D3 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D3 group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March-April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D3 group (33.5%, P < 0. 001) and in the HRT + Vit D3 group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1, 25(OH)2D) increased, however, only in the HRT group (23.7%, P < 0. 05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D3 supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D3 did not increase serum calcitriol concentrations as much as HRT alone.

Calcium↗
PubMed1998

Caries in patients with non-insulin-dependent diabetes mellitus.

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.

Aged↗
PubMed1998

Saliva in non-insulin-dependent diabetic patients and control subjects: The role of the autonomic nervous system.

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.

Aged↗
PubMed1998

Association of a leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y with high serum cholesterol and LDL cholesterol levels.

High serum levels of total and LDL cholesterol are important risk factors in the development of atherosclerotic coronary artery disease. Cholesterol metabolism is affected by nutritional, environmental and genetic factors. Neuropeptide Y (NPY), which is widely expressed in both the central and peripheral nervous systems, has an important role in the hypothalamic regulation of energy balance by stimulating food intake and favoring energy storage through increased lipoprotein lipase activity in white adipose tissue. As a part of ongoing study of the genetic basis of obesity, we screened the NPY gene for sequence variants. We report here the identification of a common Leu(7)-to-Pro(7) polymorphism in the signal peptide of NPY. Presence of this Pro(7) in NPY was associated with higher serum levels of total and LDL cholesterol in obese subjects participating in two independent Finnish and Dutch studies. Furthermore, normal-weight Finns with Pro(7) also had higher serum levels of total and LDL cholesterol than did subjects with Leu(7)/Leu(7), as analyzed in three subsequent determinations at 5-year intervals during a 10-year follow-up period. The NPY polymorphism was not associated with higher cholesterol levels in normal-weight Dutch. Our study provides evidence that NPY is linked to cholesterol metabolism and that the polymorphism producing Pro(7) in NPY is one of the strongest genetic factors identified thus far affecting serum cholesterol, particularly in obese subjects.

Adult↗
PubMed1998

Factors predictive of referral to psychiatric hospital among general hospital psychiatric consultations.

The aim of this paper was to explore the factors necessitating psychiatric hospital care in a Finnish multi-centre study of general hospital in-patients referred for psychiatric consultation. The study group consisted of 1251 patients referred to psychiatric hospital (n = 181) and a comparison group (n = 1070) consisting of subjects who were not referred. Differences between groups were studied by univariate analysis. Logistic regression analysis was used both to assess the factors contributing to referral to psychiatric hospital and to create predictive models. The validity of the models was analysed by means of receiver operating characteristic (ROC) curves in an independent sample. Psychiatric hospital care during the previous 5 years was associated with a 3.7-fold (odds ratio) increased risk of hospitalization. A diagnosis of psychosis was associated with a 2.9-fold increased risk, and attempted suicide as a reason for consultation was associated with a 2.1-fold increased risk. Not being married doubled the risk, and the odds ratio was also high in cases of poor psychosocial functioning (as assessed by Global Assessment of Functioning (GAF) score). The predictive model differentiated reasonably well between those patients who were hospitalized and the other patients. In conclusion, this multi-centre study of factors predictive of referral to psychiatric hospital among general hospital patients revealed that the most important determinants were previous psychiatric care, diagnosis of psychosis or severe depression, attempted suicide, being unmarried, and poor psychosocial functioning as assessed by GAF score.

Adult↗
PubMed1998

Age and gender dependency of baroreflex sensitivity in healthy subjects.

We evaluated the correlates of baroreflex sensitivity (BRS) in healthy subjects. The study consisted of 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Baroreflex control of heart rate was measured by using the phenylephrine bolus-injection technique. Frequency- and time-domain analysis of heart rate variability and an exercise test were performed. Plasma norepinephrine, epinephrine, insulin, and arginine vasopressin concentrations and plasma renin activity were measured. In the univariate analysis, BRS correlated with age (r = -0.65, P < 0.001), diastolic blood pressure (r = -0.47, P < 0.001), exercise capacity (r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also a significant correlation between BRS and plasma norepinephrine concentration (r = -0.22, P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to the multivariate analysis, age and gender were the most important physiological correlates of BRS. They accounted for 52% of interindividual BRS variation. In addition, diastolic blood pressure and high-frequency component of heart rate variability were significant independent correlates of BRS. BRS was significantly higher in men than in women (15.0 +/- 1.2 vs. 10.2 +/- 1.1 ms/mmHg, respectively; P < 0.01). Twenty-four percent of women > 40 yr old and 18% of men > 60 yr old had markedly depressed BRS (< 3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthy subjects. In addition, we demonstrate that BRS values that have been proposed to be useful in identifying postinfarction patients at high risk of sudden death are frequently found in healthy subjects.

Adult↗
PubMed1998

Serum uric acid is a strong predictor of stroke in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND AND PURPOSE: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased risk for stroke. Hyperuricemia is a common finding in NIDDM, but its significance as an independent risk factor for cardiovascular disease has remained uncertain. Therefore, we investigated serum urate as a predictor of stroke in NIDDM patients free of clinical nephropathy (ie, with a serum creatinine level of < or = 120 micromol/L). METHODS: In this population-based study, cardiovascular risk factors were determined in 1017 patients (551 men and 466 women) with NIDDM, aged 45 to 64 years at baseline. The patients were followed up for 7 years with respect to stroke events. RESULTS: During the follow-up period, 31 NIDDM patients (12 men [2.2%] and 19 women [4.1%]) died from stroke and 114 NIDDM patients (55 men [10.0%] and 59 women [12.7%]) had a fatal or nonfatal stroke. The incidence of stroke increased significantly by quartiles of serum uric acid levels (P<.001). High uric acid level (above the median value of > 295 micromol/L) was significantly associated with the risk of fatal and nonfatal stroke by Cox regression analysis (hazard ratio, 1.93 [1.30 to 2.86]; P=.001). This association remained statistically significant even after adjustment for all cardiovascular risk factors (hazard ratio, 1.91 [1.24 to 2.94]; P=.003). CONCLUSIONS: Our results indicate that hyperuricemia is a strong predictor of stroke events in middle-aged patients with NIDDM independently of other cardiovascular risk factors.

Cerebrovascular Disorders↗
PubMed1998

Insulin resistant phenotype is associated with high serum leptin levels in offspring of patients with non-insulin-dependent diabetes mellitus.

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.

Adipose Tissue↗
PubMed1998

Periodontal findings in elderly patients with non-insulin dependent diabetes mellitus.

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.

Aged↗
PubMed1998

Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis.

OBJECTIVE: We studied the 15-year cardiovascular mortality and morbidity of newly diagnosed patients with type 2 diabetes and of nondiabetic control subjects and the predictors of cardiovascular mortality in diabetic patients. RESEARCH DESIGN AND METHODS: We performed a 15-year prospective study of 133 middle-aged patients with newly diagnosed type 2 diabetes and 144 control subjects. Cardiovascular risk factors were assessed in both groups at baseline and after 5 and 10 years. RESULTS: Total mortality was markedly higher in patients with type 2 diabetes (total: 44.3 vs. 12.9% for men, age-adjusted odds ratio [OR] 5.0, P < 0.001; 44.4 vs. 11.0% for women, OR 5.2, P < 0.001), which was due to increased cardiovascular mortality (ORs for men and women: 6.2 and 11.2, respectively, P < 0.001 for both). The incidences of fatal and nonfatal myocardial infarction and stroke were likewise higher in diabetic patients. In univariate analyses and various multiple logistic regression analyses, hyperglycemia was a constant predictor of cardiovascular mortality assessed at the time of diagnosis or at 5- or 10-year examinations. Moreover, lipoprotein abnormalities characteristic of type 2 diabetes (low HDL cholesterol, high LDL triglycerides or apolipoprotein B levels, and low LDL cholesterol/apolipoprotein B ratio as a marker for LDL size) were predictive of cardiovascular death in these analyses. CONCLUSIONS: This long-term study of a well-characterized group of newly diagnosed patients strengthens the view that the prognosis in middle-aged subjects is markedly impaired and that both hyperglycemia and compositional lipoprotein abnormalities are predictors of cardiovascular mortality in patients with type 2 diabetes.

Age Factors↗
PubMed1997

Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects.

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.

Alleles↗