Biomedical subjects

L Niskanen

Publications and source records attributed to L Niskanen.

At least 73 records · Page 4Linked to original sources

PubMed1997

Effects of dietary fat modification on fibrinogen, factor VII, and plasminogen activator inhibitor-1 activity in subjects with impaired glucose tolerance.

Our aim was to assess the impact of a monounsaturated fat-enriched (Mono) diet and a diet recommended by the National Cholesterol Education Program (NCEP) on plasma levels of fibrinogen and activities of factor VII (FVII:C) and plasminogen activator inhibitor-1 (PAI-1) and the impact of genetic polymorphisms of these variables (HaeIII, MspI, and 4G/5G polymorphisms, respectively) in 28 subjects with impaired glucose tolerance ([IGT] 17 men and 11 women; mean age, 55.6 +/- 5.5 years). A diet rich in fat and saturated fatty acids served as a baseline diet for 3 weeks. Thereafter, subjects were randomized for the next 8 weeks to either the Mono diet (n = 12) or NCEP diet (n = 18). Fibrinogen levels or PAI-1 activities did not change with either of the diets, but fibrinogen levels were higher (3.4 +/- 0.5 v 4.0 +/- 0.6 g/L, P = .007 at baseline) throughout the study in heterozygous subjects with respect to HaeIII polymorphism. This polymorphism and age accounted for 38% of the variation of fibrinogen levels. MspI polymorphism together with body mass index explained 51% of the variation of FVII:C, which was higher in subjects with the M1M1 genotype compared with M1M2/M2M2 genotypes (127% +/- 21% v 90% +/- 12%, P < .001). FVII:C showed a decrease with the NCEP diet (P < .05), but the decline was confined to M1M1 subjects. PAI-1 activity did not differ significantly between the genotypes. The insulin sensitivity index (SI) obtained by the minimal model method was the main explanatory variable of PAI-1 activity. To conclude, despite good compliance, the fat-modified diet did not alter plasma levels of fibrinogen or PAI-1 in white subjects with IGT. FVII:C levels decreased with the NCEP diet, but this was confined to subjects with the M1M1 genotype.

Analysis of Variance↗

PubMed1997

Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients.

In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 were retrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. Better prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk of IFI after allogeneic BMT.

Acute Disease↗

PubMed1997

Serum leptin in relation to resting energy expenditure and fuel metabolism in obese subjects.

OBJECTIVE: Leptin is the product of ob gene shown to regulate body fat in mice. It is produced by human adipose tissue as well, but its physiological functions in man are not known. We explored if there is a relationship in obese humans with serum leptin and energy and fuel metabolism. DESIGN: Cross-sectional study including 45 obese (10 men, 35 women; age and body mass index: 42 +/- 7 y and 35.1 +/- 3.6 kg/m2, respectively). MEASUREMENTS: Food intake by a four-day-food record, blood samples for serum leptin concentrations and resting energy expenditure by indirect calorimetry. RESULTS: Leptin concentrations showed an inverse association (adjusted for fat mass, age and sex) with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate (r = -0.324, P < 0.05; r = -0.420, P < 0.01; r = 0.478, P = < 0.01, respectively), and interestingly, also with dietary fat intake (unadjusted r = -0.30, P < 0.05). Especially, leptin concentrations were elevated in those with low resting energy expenditure and respiratory quotient (below the median). CONCLUSION: Serum leptin concentrations in obese subjects showed an inverse association with resting energy expenditure, respiratory quotient and carbohydrate oxidation rate. The physiological significance of these associations is unclear at the moment but could indicate that obese subjects show resistance to the actions of leptin also outside the brain in terms of regulating metabolic rate and fuel metabolism.

Adult↗

PubMed1997

Altered antioxidant enzyme defences in insulin-dependent diabetic men with increased resting and exercise-induced oxidative stress.

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.

Adult↗

PubMed1997

Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus.

An initial improvement in glycemic control is often followed by gradual deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-treated NIDDM patients in the Finnish Multicenter Insulin Therapy Study who were treated with either combination therapy with insulin or insulin alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point vs. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseline body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A1c decreased almost 3-fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 kg/m2 (nonobese patients) than in those whose weight exceeded 28.1 kg/m2 (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients regardless of their treatment regimen. Insulin doses, per body weight, were similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therapy with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin therapy alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not influence weight gain in the obese group, who gained 4.4 +/- 1.0 kg during combination therapy with insulin and 4.5 +/- 1.1 kg during insulin therapy alone. We reached the following conclusions: 1) after an initial good response, glycemic control deteriorates more in obese than in nonobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin therapy, but it may induce a disproportionately large increase in insulin requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves equally during 1 yr with combination therapy with insulin and insulin alone, but combination therapy with insulin is associated with less weight gain than treatment with insulin alone; 4) weight gain appears harmful, as it is associated with increases in blood pressure and low density lipoprotein cholesterol.

Adult↗

PubMed1997

Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postmenopausal women were randomized into 4 treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the serum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the serum concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 months, but the other two markers showed no change. The only change seen in the placebo group was a 19.2% increase in OC concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively], whereas no significant changes occurred in the hormone groups. There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers (r = -0.240 through -0.336; P = 0.005-0.064). Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have only marginal effects on bone metabolism in early postmenopausal healthy women.

Alkaline Phosphatase↗

PubMed1997

Long-term vitamin D3 supplementation may have adverse effects on serum lipids during postmenopausal hormone replacement therapy.

OBJECTIVE: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. DESIGN AND METHODS: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D3 (vitamin D3 300 IU/day), (iii) HRT+Vit D3 (both as above), (iv) placebo (calcium lactate 500 mg/day). RESULTS: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the HRT group (10.1%, P<0.001) and the HRT+Vit D3 group (5.9%, P=0.005), increased in the Vit D3 group (4.1%, P=0.035) but remained unchanged in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P<0.001) and by 3.3% in the HRT+Vit D3 group (P=0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased in the Vit D3 group (5.2%, P=0.001), HRT+Vit D3 group (3.7%, P=0.046), and the placebo group (4.5%, P=0.006) but did not change significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P=0.006) and decreased in the Vit D3 group (10.5%, P<0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0-18.8%, P<0.05-0.001). CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.

Analysis of Variance↗

PubMed1997

Evolution of postpartum mental health.

We investigated the postpartum mental health of 139 mothers, 4-8 weeks after delivery and 2 years later. The sample consisted of mothers who attended a maternity center for a routine health check-up 1-2 months after delivery. The occurrence of mental disorders was assessed using a 12-item General Health Questionnaire (GHQ). The occurrence of mental disorders (> 2 on the GHQ) was 28.1% in the initial check-up and 19.4% 2 years later. Mental health improved in 27 mothers (19%) but remained impaired (i.e. cases) in 12 (9%). Mental health was normal in 85 mothers (61%) during both examinations. Factors predicting chronicity of mental disorder on univariate analysis were poor financial situation, poor social support, problems with a partner and life events perceived as stressful during follow-up. Those with continuing mental-health problems had more psychiatric problems than the others before pregnancy. Most (92%) of these subjects had not become pregnant again. Using a logistic-regression analysis, independent factors predicting chronicity of mental-health problems were the high Zung score (Odds Ratio (OR) 1.4, 95% confidence interval (CI) 1.16-1.65) and a deterioration in relationship with a partner during pregnancy (OR 29, 95% CI 1.83-460). On the other hand, a low Zung score (OR 1.3, 95% CI 1.14-1.44) after delivery predicted recovery from mental disorder. A postpartum mental disorder usually resolves spontaneously. However, mental symptoms sometimes persist. The postpartum mental-health of mothers should be assessed, and treatment provided, if necessary.

Analysis of Variance↗

PubMed1997

The Captopril Prevention Project (CAPPP) in hypertension--baseline data and current status.

The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

Adult↗

PubMed1996

Apolipoprotein E phenotype modifies metabolic and hemodynamic abnormalities related to central obesity in women.

Apolipoprotein E (apo E) is a normal constituent of very-low-density lipoproteins and it participates in the metabolism of both low-density lipoproteins (LDL) and apo E-containing lipoproteins. In the present study, the aim was to examine to what extent apo E phenotypes modify central obesity-induced changes in serum lipids, insulin, and blood pressure in obese women. Altogether, 143 middle-aged obese women with a body mass index (in kg/m2) of 28.0-43.0 were examined. Twelve had apo E 3,2 phenotype, 93 had apo E 3,3 phenotype, and 38 had either apo E 4,3 or 4,4 (4,3 + 4,4 group) phenotype. Serum total and LDL cholesterol were lower in the apo E 3,2 group than in other groups, but no significant differences were observed in other lipid variables in this regard. Both systolic and diastolic blood pressure measures tended to be lowest in subjects with apo E 3,2 phenotype and highest in those with apo E 4,3 or 4,4 phenotype (P = 0.08-0.15 for trend). When serum lipids, blood pressure, and insulin were analyzed by waist circumference and apo E phenotype group, it became evident that women who had central obesity and the apo E 4 allele had the highest blood pressures, insulin-glucose ratios, and insulin concentrations. These results suggest that apo E phenotype significantly modifies the central obesity-induced changes in metabolic and hemodynamic variables characteristic of insulin resistance.

Adult↗

PubMed1996

Factors predicting psychosocial recovery in psychiatric patients.

We examined factors associated with psychosocial recovery in patients receiving specialist psychiatric treatment by means of a questionnaire directed at staff and patients (n = 1084) in an extensive study performed in North Savo, Kuopio, Finland. Psychosocial recovery was considered to have taken place if the Global Assessment Scale (GAS) score had increased from the lowest estimate obtained during the preceding year by at least 28 points at the time of the study (n = 102). The remaining cases (n = 982) served as controls. In the univariate analysis of all of the patients, the factors associated with good recovery were a high level of basic education, a diagnosis of major depression and adequate social support. The opportunity to contact a therapist outside fixed treatment visits was also a factor predicting psychosocial recovery. In the multivariate analysis, independent factors predicting recovery were the high frequency of treatment contacts in cases of schizophrenia, previous hospitalization in major depression, and a high level of basic education and hospitalization in personality disorders.

Adaptation, Psychological↗

PubMed1996

Correlates of life satisfaction among psychiatric patients.

The aim of this study was to examine the sociodemographic and clinical variables associated with life satisfaction in psychiatric patients. The study population consisted of out-patients and in-patients (n = 1204) treated at the Department of Psychiatry of Kuopio University Hospital in North Savo, Finland, during May 1993. Sociodemographic, psychosocial and clinical correlates of life satisfaction were examined by means of two different questionnaires, one directed at patients and the other directed at the staff. Life satisfaction was assessed by means of a separate scale based on four questions. Patients with schizophrenia were less dissatisfied than patients with other disorders. The strongest correlates of dissatisfaction were depression and poor social support. Other factors relating to dissatisfaction in multiple regression analysis were self-rated health and poor financial circumstances. A psychosomatic reaction tendency or degree of psychosocial functioning at the time of the study was not independently related to life satisfaction. Psychiatric patients who are dissatisfied should be evaluated both for depression and for effectiveness of their social network.

Adult↗

PubMed1996

Autoantibodies against oxidized LDL do not predict atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus.

Accelerated atherosclerosis in diabetes has been suggested as being due to an enhanced oxidative modification of LDL. We hypothesized that the titers of autoantibodies against oxidized LDL (oxLDL) may be increased in patients with non-insulin-dependent diabetes mellitus (NIDDM) and that they may contribute to various manifestations of atherosclerosis among such patients. In a 10-year follow-up study of 91 newly diagnosed NIDDM patients and 82 nondiabetic control subjects, autoantibodies against oxLDL (expressed as the ratio of autoantibodies against oxLDL and native LDL) were measured at baseline and after 10 years. Quantitative ultrasonography to examine the intimal-medial thickness of the common carotid artery (a morphological index of arterial wall injury) and carotid bifurcation was performed at the 10-year examination. The relationship of autoantibodies against oxLDL to the occurrence of cardiovascular death, fatal and nonfatal myocardial infarction, stroke, and any cardiovascular event as well as to the intimal-medial thickness of the common carotid artery and carotid bifurcation was evaluated. Associations between these autoantibodies and metabolic variables (fasting glucose, glycosylated hemoglobin, insulin, and serum lipids) in NIDDM patients were also examined. Autoantibodies against oxLDL did not differ between NIDDM and control subjects (NIDDM: baseline, 1.63 and 0.61 to 23.6; 10-year examination, 1.64 and 0.06 to 59.0; control group: baseline, 1.84 and 0.13 to 36.0; 10-year examination, 1.50 and 0.25 to 8.29; median and range, P = .62, baseline; P = .45, 10 year). In both groups, the titers of these autoantibodies measured at baseline and after 10 years significantly correlated with each other (r = .63 for the diabetic and r = .51 for the control group, respectively, P < .001 for each). The frequency of all cardiovascular events was markedly higher in the NIDDM group than in the control group, but autoantibodies against oxLDL had no significant association with any of these events, including cardiovascular mortality. At the 10-year examination the intimal-medial thickness of the common carotid artery (1.24 +/- 0.36 versus 1.06 +/- 0.30 mm, P = .002) and carotid bifurcation (2.11 +/- 0.73 versus 1.77 +/- 0.82 mm, P = .01) were greater in NIDDM patients than in control subjects, but autoantibodies did not show any association with the intimal-medial thicknesses in either the diabetic or control groups. Autoantibodies against oxLDL indicate the presence of oxidatively modified LDL in vivo, but their titers in the serum do not seem to associate with the excess cardiovascular mortality, morbidity, or intimal-medial thickness of the carotid artery.

Arteriosclerosis↗

PubMed1996

Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus.

Medial artery calcification (MAC) is a nonobstructive condition leading to reduced arterial compliance that is commonly considered as a nonsignificant finding. The aim of our study was to investigate the predictive value of MAC in relation to 7-year cardiovascular mortality, coronary heart disease (CHD) events, stroke, and lower extremity amputation in 1059 patients (581 men and 478 women) with non-insulin-dependent diabetes mellitus (NIDDM). At baseline radiologically detectable MAC in femoral arteries was found in 439 patients (41.5%) and intimal-type calcification in 310 diabetic patients (29.3%). The mean fasting plasma glucose at baseline was somewhat higher in women and the duration of diabetes somewhat longer in patients with MAC than in those without, but otherwise the presence of MAC was unrelated to conventional cardiovascular risk factors. During the follow-up 305 diabetic patients died: 208 from cardiovascular disease, 158 from CHD, and 34 from stroke. Furthermore, 58 NIDDM patients underwent their first lower extremity amputation. MAC was a strong independent predictor of total (risk factor-adjusted odds ratio and 95% confidence interval: 1.6; 1.2, 2.2), cardiovascular (1.6; 1.1, 2.2), and CHD (1.5; 1.0, 2.2) mortality, and it was also a significant predictor of future CHD events (fatal or nonfatal myocardial infarction), stroke, and amputation. This relationship was observed regardless of glycemic control and known duration of NIDDM. MAC is a strong marker of future cardiovascular events in NIDDM unrelated to cardiovascular risk factors, supporting the hypothesis that reduced arterial elasticity could lead to clinical manifestations of diabetic macroangiopathy.

Blood Glucose↗

PubMed1996

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↗

PubMed1996

Insulin treatment in elderly patients with non-insulin-dependent diabetes mellitus. A double-edged sword?

Elderly patients with non-insulin-dependent (type 2) diabetes mellitus (NIDDM) form one of the largest sectors of the diabetic population. Emerging evidence indicates that hyperglycaemia is associated not just with an increased risk of microvascular complications but also with macrovascular disease, which remains the main cause of excess mortality in people with NIDDM. The treatment of hyperglycaemia in patients with NIDDM is notoriously difficult when diet, exercise and judicious use of oral antihyperglycaemic agents fail to maintain acceptable metabolic control. The treatment of hyperglycaemia in elderly patients is further hampered by age- or disease-related comorbidity. Insulin therapy can ameliorate many metabolic abnormalities of NIDDM, with consequent reduction of hyperglycaemia. Moreover, insulin treatment induces antiatherogenic changes in serum lipids and lipoproteins and probably enhances general well-being. However, insulin therapy is associated with bodyweight gain and an increased risk of hypoglycaemia. An unresolved question is the relationship of exogenous insulin therapy to the development of cardiovascular diseases. This reverse side of the coin has prompted research aimed at establishing methods to achieve the best possible reduction in hyperglycaemia with the smallest dose of insulin as possible. The most promising target in this respect has been the control of glucose overproduction from the liver by the nocturnal administration of intermediate- or long-acting insulin with or without oral antihyperglycaemic drugs. Intensive insulin therapy does not seem to have clear-cut benefits in elderly patients and can be hazardous. However, we cannot at present predict who will benefit from the various therapeutic regimens and therefore clinicians should use sound clinical judgment in choosing the appropriate therapy for an individual patient with NIDDM. Although we do not know at present whether we can, by our current modes of treatment, lower the frequency of vascular diseases, therapeutic nihilism, even in elderly patients with NIDDM, is outmoded.

Aged↗

PubMed1996

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↗

PubMed1996

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↗