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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 217 records · Page 12Linked to original sources
PubMed1996

Epidemiological evidence for the association of hyperglycaemia and atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) increases the risk for all manifestations of atherosclerotic vascular disease, coronary heart disease (CHD), cerebrovascular disease and peripheral vascular disease. Only a small proportion of this excess risk can be explained by the effects of conventional cardiovascular risk factors, which implies that the diabetic state or factors related to it have to play a significant role in the pathogenesis of macrovascular disease in NIDDM. Six recent prospective population-based studies including a large number of NIDDM patients have indicated that poor glycaemic control evaluated by fasting hyperglycaemia or glycosylated haemoglobin levels increases the risk for CHD, stroke and amputation independently of other risk factors. A dose-response relationship between markers of glycaemic control and the incidence of cardiovascular mortality and morbidity has been demonstrated in all these studies. However, there is so far no direct proof that strict glycaemic control would delay or prevent atherosclerotic complications.

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↗
PubMed1995

Prospective study of small LDLs as a risk factor for non-insulin dependent diabetes mellitus in elderly men and women.

BACKGROUND: The excess risk of atherosclerosis among patients with non-insulin dependent diabetes mellitus (NIDDM) is well documented. However, the presence of conventional risk factors cannot fully account for this excess risk, and the underlying mechanism remains to be elucidated. The present study prospectively evaluated the role of small LDL, a known risk factor for coronary heart disease, as a risk factor for the development of NIDDM. METHODS AND RESULTS: The study was based on a nested case-control sample of 204 elderly men and women from Kuopio, Finland. LDL subclasses were characterized by size with 2% to 14% polyacrylamide gels produced by recently developed methods. Logistic regression analysis showed that subjects with a predominance of small LDL (LDL subclass phenotype B) had a greater than two fold increased risk for developing NIDDM over the 3.5-year follow-up period. This association was independent of age, sex, glucose intolerance, and body mass index but was not independent of fasting triglyceride or insulin levels. Further, an increase of 5A in LDL diameter was associated with a 16% decrease in risk of NIDDM, and a composite variable of LDL diameter and triglyceride and HDL cholesterol concentrations, identified by principal-components analysis, was also associated with NIDDM. These associations may be attributable to the role of small LDL as a marker for insulin resistance. CONCLUSIONS: This study is the first to demonstrate that a predominance of small LDL particles is a risk factor for the future development of NIDDM, and it implies that small LDL contributes to risk of coronary heart disease in prediabetics.

Aged↗
PubMed1995

Hippocampal atrophy, acute THA treatment and memory in Alzheimer's disease.

We designed the present study to investigate the hypothesis that progression of hippocampal pathology may decrease the therapeutic effects of anti-cholinesterase drug, tetrahydroaminoacridine, on memory functioning in Alzheimer's disease (AD) patients. Memory, visuoconstructive, executive and vigilance functions were assessed after administration of placebo (p.o.; two placebo sessions) and tetrahydroaminoacridine (one session for 25 and 75 mg, p.o.). Eight patients performed better on list learning test during tetrahydroaminoacridine 75 mg than after placebo or tetrahydroaminoacridine 25 mg. The responders performed during baseline examination better than the non-responders in executive and some declarative memory functions, and had higher MMSE scores than the non-responders. The responders had larger left and right hippocampi than the non-responders. The hippocampal volume correlated with list learning performance. The results suggest that severe hippocampal atrophy may block memory improving effect of an anticholinesterase drug, tetrahydroaminoacridine.

Alzheimer Disease↗
PubMed1995

The association of apolipoprotein E polymorphism with memory: a population based study.

Several studies have shown an association between the apolipoprotein epsilon 4 allele and Alzheimer's disease (AD). The allele epsilon 2 has been associated with survival and longevity. We wanted to examine whether the relationship between cognitive efficiency and apolipoprotein E polymorphism (APOE) exists in a random sample of 916 non-demented elderly subjects. Episodic memory was examined with the list learning test, and with immediate and delayed recall of the figures. Semantic memory was examined with the Category and Verbal Fluency Tests. Constructional abilities were examined by copying the figures. Attention functions were examined with Trail Making A and B tests. We found that subjects with APOE E2/2 and 2/3 phenotypes showed better learning ability than those subjects with the APOE E2/4, 3/4 or 4/4 phenotypes. Impaired memory was not related to the excess of cardiovascular diseases in the subjects with APOE E2/4, 3/4, 4/4 phenotypes. Thus they may be associated, at least partly, with genetic factors.

Aged↗
PubMed1995

Hyperinsulinemic microalbuminuria. A new risk indicator for coronary heart disease.

BACKGROUND: Both hyperinsulinemia and microalbuminuria have been shown to increase coronary heart disease (CHD) risk, but the interaction among hyperinsulinemia, microalbuminuria, and the risk for CHD has not been investigated in previous studies. METHODS AND RESULTS: The risk of CHD in relation to hyperinsulinemia and microalbuminuria was examined in a cohort of 1069 elderly nondiabetic subjects from Kuopio, east Finland, during 3.5 years of follow-up. The overall incidence of CHD death was 2.8%, and 6.9% of study subjects died of CHD or had a nonfatal myocardial infarction (later referred to as all CHD events). In the highest fasting-insulin quintile (fasting insulin > or = 114.0 pmol/L), there was a slightly but insignificantly higher incidence rate of both CHD mortality and all CHD events compared with lower quintiles. The incidence rates of CHD mortality and all CHD events were significantly higher in the highest urinary albumin/creatinine ratio (ACR) quintile (ACR > or = 3.22 mg/mmol) compared with lower quintiles (P < .05 and P < .01, respectively). Hyperinsulinemic microalbuminuria (simultaneous presence of fasting insulin > or = 114.0 pmol/L and ACR > or = 3.22 mg/mmol) markedly increased the risk of CHD mortality (12.5%, P < .001) and all CHD events (18.8%, P < .001) compared with normoinsulinemic subjects without microalbuminuria (2.2% and 5.8%, respectively). In univariate logistic regression analyses, hyperinsulinemic microalbuminuria was a strong predictor of both CHD death (odds ratio [OR], 5.93; P < .001) and all CHD events (OR, 3.39; P = .002). Multivariate logistic regression analyses were also performed, including sex, current smoking, waist-hip ratio, systolic blood pressure, and HDL cholesterol, with insulin, ACR, or both as independent variables. Even after adjustment for these variables, hyperinsulinemic microalbuminuria remained a strong predictor of CHD death (OR, 7.91; P < .001) and all CHD events (OR, 2.95; P = .014). The group with hyperinsulinemic microalbuminuria was characterized by the most adversely affected risk factor pattern (high triglycerides > or = 2.3 mmol/L, low HDL cholesterol < or = 0.9 mmol/L in men and < or = 1.20 mmol/L in women, and hypertension). CONCLUSIONS: Simultaneous occurrence of hyperinsulinemia and microalbuminuria identifies a group of subjects with a highly increased risk for CHD in elderly nondiabetic subjects.

Aged↗
PubMed1995

Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group.

High serum level of bioactive interleukin-6 (IL-6) is regarded as a predictor of poor prognosis in multiple myeloma (MM). On the other hand, the reported levels of immunoreactive IL-6 have been highly variable, and the prognostic value of immunoreactive IL-6 in MM is not clear. We have analyzed the prognostic significance of serum immunoreactive IL-6, as measured by a sensitive immunosorbent assay, in 210 patients with newly diagnosed MM subsequently treated with intermittent melphalan and prednisone. The serum levels of acute phase proteins C-reactive protein (CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein (orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP, alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the patients, respectively. There was a significant correlation between the clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P = .001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the patients were alive. Univariate logistic regression analysis showed that high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM (P = .007), beta 2-microglobulin (beta 2M; P < .001), and thymidine kinase (P < .05) were all associated with 3-year mortality. In multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P = .01) had independent prognostic significance. The patients with high levels of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying within 3 years from diagnosis (16% and 21% of the patients in these groups were alive, respectively). When the patients were stratified according to the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT was especially evident in stage II patients. When the patients were divided into two groups according to normal or raised serum IL-6 levels, the patients with high IL-6 levels had more frequent osteolytic bone lesions (P = .03) and a more aggressive disease. We conclude that serum immunoreactive IL-6 is a significant prognostic marker in MM.

Acute-Phase Proteins↗
PubMed1995

Polymorphisms of the human hexokinase II gene: lack of association with NIDDM and insulin resistance.

Skeletal muscle and adipose tissue hexokinase II is a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the association of alleles at four polymorphic loci in this gene with NIDDM and insulin resistance in 110 Finnish diabetic patients with NIDDM and in 97 Finnish control subjects with normal glucose tolerance and a negative family history of diabetes. The four polymorphic nucleotide substitutions (silent) in the coding region of the hexokinase II gene were: GAC 251 GAT (exon 7), AAC 692 AAT and CCG 736 CCC (exon 15), and CTG 766 CTA (exon 16). Allele frequencies of each of these polymorphisms did not differ between patients with NIDDM and control subjects. In addition, subjects who were homozygous for the less frequent allele of each of the four polymorphisms had a similar degree of insulin resistance, as determined by the euglycaemic clamp technique, as did the subjects who were homozygous for the common allele in both control subjects and in patients with NIDDM. In conclusion, polymorphisms in the hexokinase II gene are not associated with the risk of NIDDM or insulin resistance in the Finnish population.

Adipose Tissue↗
PubMed1995

Does NIDDM increase the risk for coronary heart disease similarly in both low- and high-risk populations?

Finland has marked regional differences in the occurrence of coronary heart disease (CHD). Although the causes for these differences in CHD mortality and morbidity in the Finnish population are unknown, it offers an excellent opportunity to investigate the effects of non-insulin-dependent diabetes mellitus (NIDDM) on CHD risk in two populations differing significantly with respect to the occurrence of CHD. Therefore, we carried out a 7-year prospective population-based study including a large number of patients with NIDDM (East Finland: 253 men and 257 women; West Finland: 328 men, 221 women) and corresponding non-diabetic subjects (East Finland: 313 men, 336 women; West Finland: 325 men, 399 women). In both study populations the presence of NIDDM increased significantly the risk for CHD events (CHD mortality or all CHD events including CHD mortality or non-fatal myocardial infarction). Diabetic men had 3-4 fold higher and diabetic women 8-11-fold higher risk for CHD than corresponding non-diabetic subjects. Both non-diabetic and diabetic subjects had odds ratios (East vs West) for CHD events of about 2 indicating a similar East-West difference in the CHD risk. Regional difference was quite similar in men and women. These results imply that factors related to NIDDM, independently of conventional risk factors and the occurrence of atherothrombosis in the background population, must play a major role in the pathogenesis of atherosclerotic vascular disease in NIDDM diabetes.

Analysis of Variance↗
PubMed1995

Serum proinsulin levels are disproportionately increased in elderly prediabetic subjects.

Insulin resistance and impaired insulin secretion are thought to be the primary defects in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). Disproportionately increased proinsulin relative to insulin levels are suggested to be an early indicator of a failing pancreas. We examined the relationship of fasting specific insulin, proinsulin, and 32, 33 split proinsulin concentrations, and the proinsulin: insulin ration to the risk of developing NIDDM 3.5 years later in 65-74-year-old non-diabetic Finnish subjects participating in a population-based study (n=892) on diabetes and heart disease. Altogether 69 subjects developed NIDDM over a 3.5-year follow-up (cases). The cases were compared to randomly-selected gender-matched control subjects (n=69) and control subjects matched for gender, glucose tolerance status (normal or impaired), and body mass index (n=69). There were no differences in insulin concentrations between cases and random or matched control subjects [median and interquartile range: 123 (77-154), 108 (74-143), 118 (83-145) pmol/l, p=0.271]. Random control subjects had lower proinsulin and 32, 33 split proinsulin concentrations and split proinsulin: insulin ratios compared to cases [5.7 (3.8-9.0) vs 7.3 (4.8-10.0) pmol/l, p=0.005; 7.3 (4.5-13.0 vs 10.4 (7.1-18.0) pmol/l, p=0.002; 0.073 (0.057-0.110) vs 0.097 (0.060- 0.135), p=0.003]. Matched control subjects had lower proinsulin concentrations and proinsulin: insulin ratios compared to cases [5.9 (4.0-7.7) vs 7.3 (4.8-10.0) pmol/l, p=0.019; 0.048 (0.035-0.071) vs 0.064 (0.045-0.100), p=0.008]. When cases were compared to matched control subjects a 1 SD increase in baseline proinsulin: insulin ratio was associated with a 1.37-fold risk (p=0.020) of developing diabetes. Moreover, this association was independent of fasting glucose concentration at baseline. Thus, in elderly prediabetic subjects disproportionately increased proinsulin concentration, an indicator of defective insulin secretion, is associated with conversion to diabetes over a short time period.

Aged↗
PubMed1995

Metabolic defects in persistent impaired glucose tolerance are related to the family history of non-insulin-dependent diabetes mellitus.

Recent studies have suggested that the family history of non-insulin-dependent diabetes mellitus (NIDDM) influences glucose metabolism in subjects with normal glucose tolerance (NGT). However, it is not known whether the family history of NIDDM influences glucose metabolism in impaired glucose tolerance (IGT). We studied in a well-characterized group the impact of family history of NIDDM (diabetes mellitus [DM]-positive) in subjects with IGT on glucose disposal rate (GDR) measured by the euglycemic hyperinsulinemic clamp technique combined with indirect calorimetry. We recruited subjects from our previous population-based studies, and verified their glucose tolerance status twice during the follow-up period of 1 year. Subjects with NGT (n = 10) and IGT (n = 18) were comparable with respect to age, sex distribution, body mass index, smoking habits, and hypertension. As a group, IGT subjects showed lower GDR than the NGT group (28.6 +/- 12.1 v 38.9 +/- 13.6 mumol/kg/min, P < .05). IGT DM-positive subjects showed a 40% lower GDR than the NGT group (P < .05) and a 29% lower GDR than IGT DM-negative subjects (P = NS). IGT DM-positive subjects had lower glucose oxidation (P = NS, P < .01), glucose nonoxidation (P = NS, P = .01), and suppression of lipid oxidation (P = NS, P < .05) during the hyperinsulinemic euglycemic clamp as compared with IGT DM-negative and NGT groups, respectively. In conclusion, in subjects with persistent IGT, the family history of NIDDM is associated with the reduced total whole-body, oxidative, and nonoxidative GDR.

Administration, Oral↗
PubMed1995

A follow-up study of age-associated memory impairment: neuropsychological predictors of dementia.

OBJECTIVE: To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period of more than 3 years. DESIGN: Prospective cohort study. SETTING: The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland. PARTICIPANTS: A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI. MEASUREMENTS: A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group. RESULTS: Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests. CONCLUSION: The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.

Aged↗
PubMed1995

Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects.

The allele e4 (apo e4) of apolipoprotein E (apo E) has been associated with an increased risk for coronary heart disease (CHD) in cross-sectional studies in middle-aged subjects. We investigated the risk of CHD and stroke with respect to the number of apo e4 alleles in a prospective study of a Finnish nondiabetic cohort including 1067 subjects 65 to 74 years old at baseline. During the 3.5-year follow-up, CHD mortality was 2.8%, total CHD incidence 6.9%, and the cumulative occurrence of CHD (prevalence at baseline and the 3.5-year incidence combined) 17.0%. The incidence of stroke was 3.4%, and the cumulative occurrence of stroke was 6.0%. The CHD mortality was 3.4% in subjects with no apo e4 allele (n = 734), 1.7% in those with one apo e4 allele (n = 296), and 0% in subjects with two apo e4 alleles (n = 37) (P = NS between the three groups). The incidence of CHD according to the number of apo e4 alleles was 6.9% (no apo e4 alleles), 7.4% (one apo e4 allele), and 2.7% (two apo e4 alleles), and the cumulative occurrence of CHD was 16.5%, 18.6%, and 13.5%, respectively (P = NS). The incidence of stroke was 3.8% in subjects with no apo e4 allele, 2.7% in those with one apo e4 allele, and 0% in those with two apo e4 alleles (P = NS). The cumulative occurrence of stroke was 6.0%, 6.4%, and 2.7%, respectively (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland.

Aging has multiple effects on memory in normal subjects. However, information on the prevalence of age-associated memory impairment (AAMI) is scanty. We studied the prevalence of AAMI in a randomly selected population of 1,049 subjects aged 60 to 78 years from eastern Finland. Research criteria proposed by the National Institute of Mental Health (NIMH) Work Group were applied. We calculated prevalence rates for AAMI by the inclusion criteria alone (subjective and objective memory impairment and no dementia) as well as by the inclusion and exclusion criteria (evidence of any neurologic or other medical disorder that could produce cognitive deterioration) for the total study population, for both sexes, and for four age groups (60 to 64, 65 to 69, 70 to 74, and 75 to 78 years). Subjective memory impairment was present in 76.3% of the subjects. Prevalence rates for objective memory impairment ranged from 31.9 to 78.4% in individual tests. A total of 564 subjects (239 men, 325 women) were classified as having AAMI by the inclusion criteria alone, giving a prevalence rate of 53.8% (men, 57.4%; women, 51.3%). When we included the exclusion criteria, the prevalence of AAMI decreased to 38.4% (men, 42.5%; women, 35.7%). By both methods, age- and sex-specific prevalence rates were highest in the youngest group, aged 60 to 64 years, and lowest in the oldest group, aged 75 to 78 years. We conclude that the prevalence of AAMI, by the diagnostic criteria of the NIMH Work Group, is high in the elderly Finnish population.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Amino acid substitutions in hexokinase II among patients with NIDDM.

Hexokinase (HK) II plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. HKII is considered to be a promising candidate gene for non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance. Therefore, we investigated the frequency of variants in the coding region of the HKII gene in patients with NIDDM. Initial screening included a population-based sample of 40 Finnish patients with typical NIDDM, and subsequent screening included an additional 72 patients with NIDDM. By applying single-strand conformation polymorphism analysis and direct sequencing, the following amino acid substitutions were found among the 112 NIDDM patients: Ala314Val in one patient (0.9%), Arg353Cys in three patients (2.7%), and Arg775Gln substitution in three patients (2.7%). We also screened 97 subjects with completely normal glucose tolerance and a negative family history of diabetes for these mutations. The Ala314Val and the Arg353Cys substitutions were not found in control subjects, but the Arg775Gln substitution was found in two (2.1%) control subjects. None of these mutations were located close to the glucose- and ATP-binding sites of HKII. We conclude that mutations of the HKII gene are not a major etiological factor for NIDDM in the Finnish population.

Amino Acid Sequence↗