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M Laakso

Publications and source records attributed to M Laakso.

At least 91 records · Page 5Linked to original sources
PubMed2000

Long-term association of cardiovascular risk factors with impaired insulin secretion and insulin resistance.

The study aim was to investigate the association of cardiovascular risk factors with insulin resistance and impaired insulin secretion in an 8-year prospective population study in nondiabetic subjects. Cardiovascular risk factors of 271 subjects aged 16 to 61 years were measured at baseline, and insulin sensitivity and acute-phase insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and Bergman's minimal model 8 years later. In logistic regression analysis, baseline high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) cholesterol (P < .001 and P = .006, respectively), total, low-density lipoprotein (LDL), and VLDL triglycerides (P = .004, P = .048, and P = .002, respectively), apolipoprotein A1 (P = .010), and uric acid (P < .001) were associated with insulin resistance after adjustment for age and the body mass index (BMI). Systolic blood pressure (P = .042) and VLDL cholesterol (P = .018) were associated with impaired insulin secretion after adjustment for age and the BMI. This 8-year longitudinal study demonstrates that dyslipidemia, high blood pressure, and uric acid are associated with insulin resistance, whereas high systolic blood pressure and VLDL cholesterol are associated with impaired first-phase insulin secretion.

Adolescent↗
PubMed2000

Leucine 7 to proline 7 polymorphism in the neuropeptide y gene is associated with retinopathy in type 2 diabetes.

In this study we tested the hypothesis that the Leu7Pro7 polymorphism in prepro neuropeptide Y (NPY) gene could be a risk marker for the development of diabetic retinopathy and analyzed a well characterized cohort of patients with Type 2 diabetes followed-up for 10 years from the time of diagnosis. The frequency of Leu7/Pro7-polymorphism was 9.3% (8 out of 86). At baseline, the frequency of retinopathy in patients with the Leu7/Pro7-polymorphism was 25% (2 out of 8) and in those without it 6.4% (5 out of 78) (p=0.126). At 10-year the respective figures were 88% and 50% (p=-0.040). The odds ratio for Leu7/Pro7-polymorphism in logistic regression analysis adjusted for age, gender and HbA1c was 8.97 (95% confidence intervals 1.09-98.0; p=0.049). Our finding based on elderly Finnish Type 2 diabetic subjects suggests that the Leu7Pro7-genotype in preproNPY gene is associated with the development of diabetic retinopathy.

Aged↗
PubMed2000

Depression after coronary heart disease events.

OBJECTIVE: To study the prevalence of depression at least 6 months after various coronary heart disease (CHD) events (bypass grafting, coronary angioplasty, myocardial infarction, myocardial ischaemia without infarction) and the associations between depression and clinical variables. DESIGN: In the course of the study 414 (284 males, 130 females) patients younger than 71 years (mean age for men 60.9 years and for women 63.6 years) were interviewed and examined. Smoking habits, body mass index, lipid levels and diabetic status were recorded. The New York Heart Association (NYHA) class was assessed. Depression was screened using a self-rated depression scale. RESULTS: In the four diagnostic categories, one-sixth of the patients (14-19%) suffered from depression. Depression was associated with smoking (OR 1.7, 95% CI 1.2; 2.4) and poor NYHA class (OR 1.9, 95% CI 1.4; 2.6). CONCLUSION: Depression is common after CHD events, and is associated with smoking and poor NYHA class. The identification and treatment of depression should be one of the elements in the rehabilitation of cardiac patients.

Cholesterol↗
PubMed2000

Evidence for physiological coupling of insulin-mediated glucose metabolism and limb blood flow.

We hypothesized that the vasodilation observed during insulin stimulation is closely coupled to the rate of glucose metabolism. Lean (L, n = 13), obese nondiabetic (OB, n = 13), and obese type 2 diabetic subjects (Type 2 DM, n = 16) were studied. Leg blood flow (LBF) was examined under conditions of euglycemic hyperinsulinemia (EH) and hyperglycemic hyperinsulinemia (HH), which produced a steady-state whole body glucose disposal rate (GDR) of approximately 2,000 micromol. m(-2). min(-1). At this GDR, under both conditions, subjects across the range of insulin sensitivity exhibited equivalent LBF (l/min EH: L, 0.42 +/- 0.03; OB, 0.43 +/- 0. 03; Type 2 DM, 0.38 +/- 0.07; P = 0.72 by ANOVA. HH: L, 0.44 +/- 0. 04; OB, 0.39 +/- 0.05; Type 2 DM, 0.41 +/- 0.04; P = 0.71). The continuous relationship between LBF and GDR did not differ across subject groups [slope x 10(-5) l/(micromol. m(-2). min(-1)) by ANOVA. EH: L, 8.6; OB, 9.2; Type 2 DM, 7.9; P = 0.91. HH: L, 4.2; OB, 2.5; Type 2 DM, 4.1; P = 0.77], although this relationship did differ between the EH and HH conditions (P = 0.001). These findings support a physiological coupling of LBF and insulin-mediated glucose metabolism. The mechanism(s) linking substrate delivery and metabolism appears to be intact in insulin-resistant states.

Adult↗
PubMed2000

Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients.

Insulin resistance has been associated with hypertriglyceridemia, combined hyperlipidemia, and familial combined hyperlipidemia (FCHL). Whether all FCHL patients with different types of dyslipidemia have low insulin sensitivity has not been evaluated. We measured insulin sensitivity by the hyperinsulinemic euglycemic clamp with indirect calorimetry in 110 healthy controls and in 105 nondiabetic, FCHL family members: in 50 without dyslipidemia, in 19 with hypercholesterolemia (total cholesterol >/=7.7 mmol/L), in 22 with hypertriglyceridemia (total triglycerides >/=2.4 mmol/L in men 2.4 mmol/L in women), and in 14 with combined hyperlipidemia. During the hyperinsulinemic clamp, FCHL family members had higher free fatty acid levels than did controls (0.06+/-0.06 [mean+/-SD] in controls versus 0.16+/-0.11 in relatives without dyslipidemia versus 0.15+/-0. 07 in hypercholesterolemic patients versus 0.29+/-0.14 in hypertriglyceridemic patients versus 0.27+/-0.17 mmol/L in patients with combined hyperlipidemia; P<0.001 after adjustment for age, sex, and body mass index). Relatives without dyslipidemia (16.4+/-4.4 micromol. kg(-1). min(-1), P=0.001) and patients with hypertriglyceridemia (12.8+/-3.8 micromol. kg(-1). min(-1), P<0.001) and with combined hyperlipidemia (13.7+/-3.1 micromol. kg(-1). min(-1), P<0.001) had lower rates of insulin-stimulated glucose oxidation than did controls (19.4+/-4.7 micromol. kg(-1). min(-1)). Also, the rates of nonoxidative glucose disposal were lower in patients with hypertriglyceridemia (P=0.001) and combined hyperlipidemia (P=0.011) than in controls. In contrast, subjects with hypercholesterolemia and control subjects had similar rates of insulin-stimulated glucose uptake. We conclude that a defect in free fatty acid suppression during hyperinsulinemia, probably located in adipose tissue, is characteristic for all FCHL patients with varying types of dyslipidemia, whereas insulin resistance in skeletal muscle is observed only in FCHL patients with elevated triglyceride levels.

Adult↗
PubMed2000

Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.

The interpretation of conventional multivariate analyses concerning the relation of insulin to the risk of atherosclerotic disease is complex because of correlations of insulin with other risk factors. Therefore, we applied factor analysis to study the clustering of risk factors in the baseline data of the Helsinki Policemen Study (970 healthy men aged 34 to 64 years) and investigated whether these clusterings predict coronary heart disease (CHD) and stroke risk. Areas under the glucose and insulin response curves (AUC glucose and AUC insulin) were used to reflect glucose and insulin levels during oral glucose tolerance tests. During the 22-year follow-up, 164 men had a CHD event, and 70 men had a stroke. Factor analysis of 10 risk factor variables produced 3 underlying factors: insulin resistance factor (comprising body mass index, subscapular skinfold, AUC insulin, AUC glucose, maximal O(2) uptake, mean blood pressure, and triglycerides), lipid factor (cholesterol and triglycerides), and lifestyle factor (physical activity and smoking). In multivariate Cox models, the age-adjusted hazard ratio for insulin resistance factor during the 22-year follow-up was 1.28 (95% CI 1.10 to 1.50) with regard to CHD risk and 1.64 (95% CI 1.29 to 2.08) with regard to stroke risk. Lipid factor predicted the risk of CHD but not that of stroke, and lifestyle factor predicted a reduced CHD risk. Factor analysis including only 6 risk factor variables proposed to be central components of insulin resistance syndrome (body mass index, subscapular skinfold, AUC insulin, AUC glucose, mean blood pressure, and triglycerides) produced only a single insulin resistance factor that predicted the risk of CHD and stroke independently of other risk factors.

Adult↗
PubMed2000

G-250A substitution in promoter of hepatic lipase gene is associated with dyslipidemia and insulin resistance in healthy control subjects and in members of families with familial combined hyperlipidemia.

Low activity of hepatic lipase (HL) has been associated with high levels of triglycerides and high density lipoproteins, but the association of the HL promoter variants with insulin sensitivity has not been investigated. Therefore, in this study, the relationship of the G-250A promoter variant of the HL gene to the rates of insulin-stimulated glucose uptake measured by the hyperinsulinemic euglycemic clamp was investigated in 110 control subjects (82 men and 28 women, aged 50.7+/-7.6 [mean+/-SD] years, body mass index 26. 1+/-3.6 kg/m(2)) and in 105 first-degree relatives (65 men and 40 women, aged 47.8+/-16.0 years, body mass index 26.9+/-5.3 kg/m(2)) of 34 families with familial combined hyperlipidemia (FCHL). The A-250 allele of the HL promoter was associated with low rates of insulin-stimulated whole-body nonoxidative glucose disposal in control subjects (41.1+/-12.7 micromol. kg(-1). min(-1) in subjects with the G-250G genotype, 36.9+/-13.1 micromol. kg(-1). min(-1) in subjects with the G-250A genotype, and 29.9+/-13.5 micromol. kg(-1). min(-1) in subjects with the A-250A genotype; P=0.012 adjusted for age and sex) and with low rates of insulin-stimulated whole-body glucose oxidation in FCHL family members (16.7+/-4.2 versus 15.0+/-4. 4 versus 14.1+/-4.4 micromol. kg(-1). min(-1), P=0.024). In addition, the A-250 allele was associated with high levels of fasting insulin (P=0.047), very low density lipoprotein cholesterol (P=0.007), and total (P=0.009) and very low density lipoprotein (P=0.005) triglycerides in control subjects and with high levels of low density lipoprotein triglycerides (P=0.001) in FCHL family members (n=340). We conclude that the G-250A promoter variant of the HL gene is associated with dyslipidemia and insulin resistance. Mechanisms via which this polymorphism could affect insulin sensitivity remain to be elucidated.

Adult↗
PubMed2000

Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.

ATP-sensitive potassium channels play a major role in linking metabolic signals to the exocytosis of insulin in the pancreatic beta cell. These channels consist of two types of protein subunit: the sulfonylurea receptor SUR1 and the inward rectifying potassium channel Kir6.2. Mutations in the genes encoding these proteins are the most common cause of congenital hyperinsulinism (CHI). Since 1973, we have followed up 38 pediatric CHI patients in Finland. We reported previously that a loss-of-function mutation in SUR1 (V187D) is responsible for CHI of the most severe cases. We have now identified a missense mutation, E1506K, within the second nucleotide binding fold of SUR1, found heterozygous in seven related patients with CHI and in their mothers. All patients have a mild form of CHI that usually can be managed by long-term diazoxide treatment. This clinical finding is in agreement with the results of heterologous coexpression studies of recombinant Kir6.2 and SUR1 carrying the E1506K mutation. Mutant K(ATP) channels were insensitive to metabolic inhibition, but a partial response to diazoxide was retained. Five of the six mothers, two of whom suffered from hypoglycemia in infancy, have developed gestational or permanent diabetes. Linkage and haplotype analysis supported a dominant pattern of inheritance in a large pedigree. In conclusion, we describe the first dominantly inherited SUR1 mutation that causes CHI in early life and predisposes to later insulin deficiency.

ATP-Binding Cassette Transporters↗
PubMed2000

Leucine 7 to proline 7 polymorphism in the neuropeptide Y gene is associated with enhanced carotid atherosclerosis in elderly patients with type 2 diabetes and control subjects.

We have recently demonstrated that subjects having Pro7 in the signal peptide ofneuropeptide Y (NPY) have higher serum cholesterol and apolipoprotein B levels than individuals with wild-type (Leu7Leu7) signal peptide sequence. We investigated the association of Leu7Pro polymorphism with common carotid intima media thickness (IMT) assessed by ultrasonograph in patients with type 2 diabetes (n = 81; 41 men and 40 women; mean age, 67.1 yr) and nondiabetic subjects (n = 105; 48 men and 57 women; mean age, 65.5 yr) and genotyped for the Leu7Pro polymorphism in prepro-NPY. The frequency of Pro7 in prepro-NPY was 9.9% (8 of 81) in diabetic patients and 14.3% (15 of 105) in control subjects (P = 0.360). The mean common carotid IMT was 1.04 +/- 0.02 mm in nondiabetic subjects without the Leu7Pro polymorphism and 1.14 +/- 0.04 mm in nondiabetic subjects with in (P = 0.156) and 1:18 +/- 0.03 and 1.58 +/- 0.21mm in diabetic patients without and with the Leu7Pro polymorphism (P = 0.004), respectively. In the analysis of covariance of the entire group, the mean common carotid IMT was independently associated with the Leu7Pro polymorphism (F = 5.165; P = 0.024) after adjustment for known risk factors. Thus, the presence of the Pro7 substitution in the prepro-NPY associates with increased carotid atherosclerosis.

Aged↗
PubMed2000

Hyperproinsulinemia is not a characteristic feature in the offspring of patients with different phenotypes of type II diabetes.

OBJECTIVE: The purpose of this work was to study whether there are differences in plasma proinsulin levels and proinsulin-to-specific insulin ratio in the offspring of patients with different phenotypes of type II diabetes. DESIGN: Eleven glucose-tolerant offspring of type II diabetic patients with deficient insulin secretion phenotype (IS group), nine glucose-tolerant offspring of patients with insulin-resistant phenotype (IR group), and fourteen healthy control subjects without a family history of diabetes were studied. METHODS: Plasma specific insulin, plasma proinsulin, and plasma C-peptide levels were measured during a 2-h oral glucose tolerance test and during hyperglycemic clamp. RESULTS: Plasma proinsulin levels during the oral glucose tolerance test and the hyperglycemic clamp did not differ among the study groups. The IR group had a lower fasting plasma proinsulin-to-specific insulin ratio (10.3+/-1.7%) than the control group (15.4+/-1.4%; P<0.05) and the IS group (18.6+/-2.7%; P<0.05). Furthermore, the IR group had lower plasma proinsulin-to-specific insulin ratio at 30, 60 and 90 min after the oral glucose load than the IS group. However, there were no significant differences in proinsulin-to-C-peptide ratio during the oral glucose tolerance test among the study groups. In stepwise multiple regression analysis, hepatic specific insulin extraction in the fasting state (beta =0.65; P<0.001) and fasting blood glucose (beta =0.32; P<0.05) together explained 52% of the variation in fasting plasma proinsulin-to-specific insulin ratio. CONCLUSIONS: Hyperproinsulinemia is not a characteristic finding in glucose-tolerant offspring of type II diabetic probands with deficient insulin secretion or insulin-resistant phenotype. The differences in proinsulin-to-specific insulin ratios were most likely explained by different hepatic extraction among the study groups.

Adult↗
PubMed2000

Gene encoding the catalytic subunit p110beta of human phosphatidylinositol 3-kinase: cloning, genomic structure, and screening for variants in patients with type 2 diabetes.

Phosphatidylinositol (PI) 3-kinase is a key signaling molecule in insulin-stimulated glucose transport. Therefore, we investigated the catalytic subunit p110beta, of human PI 3-kinase as a candidate gene for type 2 diabetes. Human p110beta gene was cloned from the placental genomic library. All 22 exons, intronic regions flanking the exons and 1.5 kb of the proximal/5' region of the p110beta gene, were screened for variants by single-strand conformation polymorphism analysis in 79 Finnish patients with type 2 diabetes . Allele frequencies of the variants were also determined in 77 nondiabetic control subjects. No variants were found in exons in diabetic patients. However, we identified two nucleotide polymorphisms in the proximal/5' region of the p110beta gene and a variation in the number of 2-bp repeat sequence (TA)n in intron 4. The allele frequencies did not differ between diabetic and control subjects. Our results may indicate that the catalytic subunit p110beta of PI 3-kinase plays such a fundamental role in the insulin-signaling pathway that structural variants are not likely to exist in that gene. The importance of the polymorphisms in the proximal/5' region of the p110beta gene for insulin signaling remains to be determined.

Alleles↗
PubMed2000

Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin.

OBJECTIVE: To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects. RESEARCH DESIGN AND METHODS: The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment-length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects. RESULTS: In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P1 = 0.024 and P2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P1 = 0.009 and P2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects. CONCLUSIONS: These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.

ATP-Binding Cassette Transporters↗
PubMed2000

Variants in the hepatocyte nuclear factor-1alpha and -4alpha genes in Finnish and Chinese subjects with late-onset type 2 diabetes.

OBJECTIVE: To determine the role of the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in the etiology of late-onset type 2 diabetes in Finnish and Chinese subjects. RESEARCH DESIGN AND METHODS: The whole coding regions of the genes encoding for HNF-1alpha and HNF-4alpha, including approximately 800 bp of the HNF-1alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptide 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-strand conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism analysis in additional samples of 100 Finnish diabetic patients and 82 Finnish control subjects and in 58 Chinese diabetic patients and 51 Chinese control subjects. RESULTS: No previously reported gene defects were detected, but one novel functionally silent GCC-->GCG variant (nucleotide 73, exon 10) was observed in the HNF-4alpha gene in a Chinese diabetic patient. Interestingly, the Ala98Val substitution of the HNF-1alpha gene occurred at a significantly higher frequency in 140 Finnish diabetic patients compared with 82 control subjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucose tolerance tests in subjects with normal (n = 295) or impaired (n = 38) glucose tolerance. CONCLUSIONS: Variants in the HNF-1alpha and HNF-4alpha genes are unlikely to play a major role in the pathogenesis of late-onset type 2 diabetes in Finnish and Chinese subjects. However, the association of the Ala98Val variant of the HNF-1alpha gene with type 2 diabetes in Finnish subjects may indicate a diabetogenic locus close to the HNF-1alpha gene.

Adult↗
PubMed2000

MspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease.

OBJECTIVE: Elevated HDL cholesterol and its principal carrier protein apolipoprotein a1 [apo(a1)] are associated with reduced risk of coronary heart disease (CHD). No studies are available on the impact of the -75-bp and/or +83-bp polymorphisms of the apo(a1) gene on HDL cholesterol and apo(a1) levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We determined the prevalence of the: -75-bp and +83-bp polymorphisms of the apo(a1) gene by restriction fragment length polymorphism analysis among 308 unrelated nondiabetic subjects with CHD and among 251 unrelated patients with type 2 diabetes with CHD and in randomly selected 82 healthy men (CHD-). RESULTS: The rare M1- and M2- allele frequencies of the apo(a1) gene were 23 and 1.8%, respectively, among control subjects; 20 and 1.5%, respectively, among nondiabetic subjects with CHD; and 22 and 2.6%, respectively, among patients with type 2 diabetes and CHD (NS). Nonsmoking nondiabetic subjects with CHD having the M2+- genotype had higher HDL cholesterol (1.48 +/- 0.19 vs. 1.23 +/- 0.02 mmol/l, P < 0.01) and apo(a1) (1.43 +/- 0.10 vs. 1.36 +/- 0.02 g/l, P < 0.05) levels than subjects with the M2++ genotype, even after adjustment for confounding factors. This association was not found among patients with type 2 diabetes and CHD. CONCLUSIONS: We conclude that the +83-bp polymorphism of the apo(a1) gene is associated with elevated HDL cholesterol and apo(a1) levels in Finnish nondiabetic subjects but not in patients with type 2 diabetes.

Apolipoprotein A-I↗
PubMed2000

Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study.

OBJECTIVE: To investigate the association of plasma insulin with all-cause, cardiovascular, and noncardiovascular mortality. RESEARCH DESIGN AND METHODS: We studied 22-year mortality data from the Helsinki Policemen Study The study population comprised 970 men, 34-64 years of age, who were free of coronary heart disease, other cardiovascular disease, and diabetes. Area under the insulin response curve (AUC insulin) during an oral glucose tolerance test was used to reflect plasma insulin levels. RESULTS: During the follow-up period, 276 men died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI 1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97) during the entire 22 years; adjusting for other risk factors, the HR was 1.88 (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67 (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03-5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped association was observed between insulin and noncardiovascular mortality, multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively CONCLUSIONS: Hyperinsulinemia was associated with increased all-cause and cardiovascular mortality in Helsinki policemen independent of other risk factors, although these associations weakened with the lengthening of the follow-up period. The association of insulin with noncardiovascular mortality was U-shaped.

Adult↗
PubMed2000

Verbal fluency activates the left medial temporal lobe: a functional magnetic resonance imaging study.

Verbal fluency tests (VFTs) are suggested to assess frontal lobe function. This view is supported by functional imaging studies that report left frontal activation during VFTs. VFTs require retrieval of semantically associated words from long-term memory storage. The neural networks that participate in this process, however, are largely unknown. These neural networks are of interest, given that patients with early Alzheimer's disease, typically without frontal pathology, are often impaired in VFTs. In the present study, functional magnetic resonance imaging was performed to determine brain activation areas during VFTs in young subjects. In the activation task, category fluency was contrasted with orderly listing of numbers. As judged from using this comparison, there was activation in the left medial temporal lobe, in the inferior frontal and retrosplenial cortices bilaterally, and in the left superior parietal lobule. Left medial temporal lobe activation was present in 13 of the 14 study subjects either in the hippocampal formation (11 of 14) or in the posterior parahippocampal gyrus (12 of 14). These results suggest that the medial temporal lobe is required for the process of retrieval by category. Functional magnetic resonance imaging combined with a category fluency task may provide a new method to study patients with early Alzheimer's disease.

Adult↗