Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 145 records · Page 8Linked to original sources

PubMed1998

Driving experience and perception of the lead car's braking when looking at in-car targets.

Perception of the lead car's braking was measured on-road when subjects of various levels of driving experience were looking at a digital display located at the lower part of the windscreen, at the speedometer level, or in the mid-console. The brake lights of the lead car were either working normally or switched off. The results indicated that the detection of the lead car's brake lights, in daylight, is substantially impaired when a following driver is looking at the speedometer area and brake lights do not contribute to detection at all when he/she is looking at a target in the mid-console. Driving experience did not influence performance in detecting a closing headway in peripheral vision, in contrast to improvement in lane-keeping found in an earlier study. It is suggested that such differential ability in using peripheral vision for lane and distance-keeping may mislead experienced drivers when they follow another vehicle and perform certain in-car tasks.

Adult↗

PubMed1998

Epidemiology of risk factors for cardiovascular disease in diabetes and impaired glucose tolerance.

Diabetes mellitus is a strong risk factor for all manifestations of atherosclerotic vascular disease, coronary heart disease (CHD), cerebrovascular disease and peripheral vascular disease. Diabetes can be classified into two main subtypes, insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus (NIDDM). This review focuses only on NIDDM. Also, in impaired glucose tolerance (IGT), a precursor stage of diabetes, the risk of macrovascular disease is substantially increased. NIDDM and IGT are known to be associated with several adverse cardiovascular risk factors, including hypertension, obesity, central obesity, hyperinsulinemia and serum lipid and lipoprotein abnormalities, characterized mainly by elevated serum total triglycerides and low high-density lipoprotein cholesterol. Practically no information is available on the role of different cardiovascular risk factors to predict macrovascular complications in subjects with IGT. The role of different cardiovascular risk factors with respect to the risk of CHD, stroke and peripheral vascular disease will be discussed.

Cardiovascular Diseases↗

PubMed1998

Different regulation of free fatty acid levels and glucose oxidation by the Trp64Arg polymorphism of the beta3-adrenergic receptor gene and the promoter variant (A-3826G) of the uncoupling protein 1 gene in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is characterized by variable expression of dyslipidemias and insulin resistance. Because the genetic background for FCHL is unknown, we investigated the effect of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene and the promoter variant A --> G (-3826) of the uncoupling protein 1 (UCP1) gene on glucose and lipid metabolism in FCHL families. Both polymorphisms were screened in 228 members from 27 families with FCHL and in 82 control men from a random population sample. The frequency of the polymorphisms of the beta3-AR and UCP1 genes did not differ between patients with FCHL and controls. Although the rate of insulin-stimulated whole-body glucose uptake evaluated by the euglycemic clamp in family members of patients with FCHL was unaffected by both polymorphisms, subjects with the Trp64Arg genotype of the beta3-AR gene had higher rates of glucose oxidation (17.6+/-4.5 v 15.8+/-4.1 micromol/kg/min, P=.017) and lower levels of free fatty acids (FFAs) in the fasting state (0.56+/-0.27 v 0.61+/-0.28 mmol/L, P=.027) and during the euglycemic clamp (0.12+/-0.10 v 0.21+/-0.15 mmol/L, P=.041) than subjects with the Trp64Trp genotype. We conclude that in FCHL families, codon 64 polymorphism of the beta3-AR gene may influence the rate of glucose oxidation via FFA levels.

Abdomen↗

PubMed1998

Hypertension and macrovascular disease--the killing fields of NIDDM.

Diabetes mellitus and particularly non-insulin-dependent diabetes mellitus (NIDDM) increases the risk for all manifestations of: (a) atherosclerotic vascular disease; (b) coronary heart disease (CHD); (c) cerebrovascular disease; and (d) peripheral vascular disease. NIDDM is known to be associated with several adverse cardiovascular risk factors, including: (i) hypertension; (ii) obesity; (iii) central obesity; (iv) hyperinsulinemia; and (v) serum lipid and lipoprotein abnormalities, characterized mainly by elevated serum total triglycerides and low high-density lipoprotein cholesterol. This review will discuss the prevalence of hypertension in NIDDM, the role of hypertension to increase the risk for macrovascular complications in NIDDM and finally trial evidence for the beneficial effect of blood pressure lowering in patients with NIDDM.

Arteriosclerosis↗

PubMed1998

Tetrahydroaminoacridine improves the recency effect in Alzheimer's disease.

We investigated the effects of a single administration of tetrahydroaminoacridine (25 and 50 mg, orally), a cholinesterase inhibitor, on memory function in Alzheimer's disease patients. The recall of memory items from the end of the word list (recency effect) was improved in a subgroup of Alzheimer's disease patients (responders 10 out of 28) by tetrahydroaminoacridine 50 mg. However, tetrahydroaminoacridine 50 mg had no effect on the recall of those words from the beginning or middle of the list. Tetrahydroaminoacridine did not markedly improve non-verbal delayed matching to sample or paired associates learning in any of the Alzheimer's disease patients. The "responders" performed better than the "non-responders" in tests measuring memory and frontal functions. The responders had less severe hippocampal atrophy and less prefrontal blood flow defect, and had a lower frequency of the apolipoprotein E4 allele than the "non-responders". These results suggest that acute tetrahydroaminoacridine treatment may stimulate the recency effect, and that a severe dysfunction of hippocampus and prefrontal regions blocks this effect of tetrahydroaminoacridine on short-term memory performance.

Aged↗

PubMed1998

A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.

Adult↗

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

Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23.

More than half of the patients with angiographically confirmed premature coronary heart disease (CHD) have a familial lipoprotein disorder. Familial combined hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a prevalence of 1.0-2.0%. FCHL is estimated to cause 10-20% of premature CHD and is characterized by elevated levels of cholesterol, triglycerides, or both. Attempts to characterize genes predisposing to FCHL have been hampered by its equivocal phenotype definition, unknown mode of inheritance and genetic heterogeneity. In order to minimize genetic heterogeneity, we chose 31 extended FCHL families from the isolated Finnish population that fulfilled strictly defined criteria for the phenotype status. We performed linkage analyses with markers from ten chromosomal regions that contain lipid-metabolism candidate genes. One marker, D1S104, adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod score of Z = 3.50 assuming a dominant mode of inheritance. Multipoint analysis combining information from D1S104 and the neighbouring marker D1S1677 resulted in a lod score of 5.93. Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23. A second paper in this issue (Castellani et al.) reports the identification of a mouse combined hyperlipidaemia locus in the syntenic region of the mouse genome, thus further implicating a gene in this region in the aetiology of FCHL.

Adult↗

PubMed1998

Efficacy of antiplatelet treatment in hypertensive patients with TIA or stroke.

We performed a subgroup analysis of the first European Stroke Prevention Study including 1,306 patients recruited in a single center, Kuopio, Finland, to investigate whether or not antiplatelet therapy is effective in the secondary prevention of stroke in hypertensive patients with transient ischemic attack (TIA) or stroke. The patients were treated with aspirin, 990 mg/day, plus dipyridamole, 225 mg/day, or placebo for 2 years. The patients with high systolic blood pressure (> or = 140 mm Hg; n = 1.105) or high diastolic blood pressure (> or = 85 mm Hg; n = 1,120) at entry, were classified into subgroups by blood pressure level. The effect of treatment was statistically significant in all subgroups with high systolic (end-point reduction, 55.2-68.2%) and diastolic blood pressure (end-point reduction, 47.3-82.1%). Risk reduction was, however, greatest in patients with the highest diastolic blood pressure. One possible explanation is that platelets are more activated in these patients, and this can be effectively prevented by antiplatelet therapy. Further studies are needed to confirm this hypothesis.

Aspirin↗

PubMed1998

Impaired insulin-stimulated glucose oxidation and free fatty acid suppression in patients with familial combined hyperlipidemia: a precursor defect for dyslipidemia?

Familial combined hyperlipidemia (FCHL) is characterized by hyperlipidemia and insulin resistance, but intracellular defect in insulin action is unknown. Therefore, we investigated insulin action by applying the hyperinsulinemic euglycemic clamp technique with indirect calorimetry in 58 FCHL family members (28 with FCHL; 30 without dyslipidemia; aged 49+/-12 years; body mass index [BMI], 25. 2+/-4.0 kg/m2) and in 72 healthy control subjects (aged 54+/-6 years; BMI, 26.3+/-3.1 kg/m2). In the fasting state, FCHL patients had higher levels of total cholesterol, total triglycerides, and apolipoprotein B than control subjects (P<0.001 after adjustment for gender, age, and BMI). During the euglycemic clamp, FCHL patients had lower rates of glucose oxidation (15.93+/-3.55 versus 19.65+/-4. 60 micromol/kg/min; P=0.001) and higher rates of lipid oxidation (0. 15+/-0.13 versus 0.01+/-0.25 mg/kg/min; P=0.024), as well as higher levels of serum-free fatty acids (FFA) (0.24+/-0.17 versus 0.06+/-0. 06 mmol/L; P<0.001) compared with those of control subjects. Relatives without dyslipidemia differed similarly from control subjects with respect to rates of glucose and lipid oxidation and FFA suppression during the hyperinsulinemic clamp. In FCHL family members, during the euglycemic clamp FFAs correlated negatively with the rates of glucose oxidation (P<0.001) but not with the rates of glucose nonoxidation (P=0.408). In FCHL family members without dyslipidemia and in control subjects, FFAs during the clamp correlated positively with levels of total triglycerides (P<0.001) and very low density lipoprotein cholesterol (P=0.008). We conclude that in patients with FCHL, and also in their first-degree relatives, insulin's suppressive effect on FFA levels is impaired, which may precede dyslipidemia in FCHL.

Adult↗

PubMed1998

Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene.

Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to affect the affinity of intestinal FABP for fatty acids. This could cause changes in postprandial triglyceride metabolism. In the present study, postprandial lipemia was studied in normotriglyceridemic subjects with genetic variation in the FABP2 gene. Oral fat-loading tests were performed in 8 subjects homozygous for the Thr-encoding allele at codon 54 of the FABP2 gene and in 7 subjects homozygous for the Ala-encoding allele (wild type). There were no significant differences between these 2 groups in age, body mass index, fasting plasma triglyceride and cholesterol levels, or fasting glucose and insulin levels. The increase of plasma triglyceride concentration after the fat test meal was significantly greater in subjects who were homozygous for the Thr-54 allele (area under the response curve, 4.27+/-1.31 versus 2.49+/-1.18 mmol/L x h-1, P=0.04). The difference was seen in both chylomicron (2.51+/-0. 98 versus 1.41+/-0.74 mmol/L x h-1, P=0.03) and very low-density lipoprotein triglycerides (1.57+/-0.77 versus 0.99+/-0.40 mmol/L x h-1, P=0.04). Postprandial triglyceride response correlated with fasting triglycerides in the Ala-54 homozygotes (r=0.79, P=0.05) but not in the Thr-54 homozygotes (r=0.09), who showed a strong correlation between triglyceride and insulin responses (r=0.83, P=0. 02). With reservations related to a small number of subjects studied, these results indicate that the Thr-encoding allele of the FABP2 gene is associated with increased postprandial lipemia. The lipemic response was associated with postprandial insulin response, suggesting that in the Thr-54 homozygotes, altered postprandial lipemia may also modify insulin action or vice versa.

Carrier Proteins↗

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

Hyperinsulinemia and the risk of stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study.

BACKGROUND AND PURPOSE: Several studies have shown that hyperinsulinemia is associated with the risk of coronary heart disease, but information on the association of hyperinsulinemia with the risk of stroke is limited. We investigated the association of hyperinsulinemia with the risk of stroke during a 22-year follow-up of the Helsinki Policemen Study population. METHODS: The study was based on a cohort of 970 men aged 34 to 64 years who were free of cerebrovascular disease, other cardiovascular disease, or diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the insulin response curve during oral glucose tolerance test was used as a composite variable reflecting plasma insulin levels. RESULTS: During the 22-year follow-up, 70 men had a fatal or nonfatal stroke. Hyperinsulinemia (highest area under the insulin response curve quintile compared with the combined 4 lower quintiles) was associated with the risk of stroke (age-adjusted hazard ratio, 2.12; 95% CI, 1.28 to 3.49), but not independently of other risk factors (multiple-adjusted hazard ratio, 1.54; 95% CI, 0.90 to 2.62), which was mainly due to the impact of obesity, particularly upper body obesity, with subscapular skinfold thickness used as an index. Of other risk factors, upper body obesity, blood pressure, and smoking were independent predictors of the risk of stroke. CONCLUSIONS: Hyperinsulinemia was associated with the risk of stroke in Helsinki policemen during the 22-year follow-up, but not independently of other risk factors, particularly upper body obesity.

Adult↗

PubMed1998

Additive effects of the mutations in the beta3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women.

This study examined whether the Trp64Arg mutation in the beta3-adrenergic receptor (beta3AR) and the A-->G mutation in the uncoupling protein-1 (UCP-1) genes have associations with weight loss and subsequent weight maintenance. Seventy-seven obese (body mass index range, 29-46 kg/m2), clinically healthy, premenopausal women were studied. A 12-wk weight reduction by very low calorie diet (VLCD) was followed by a 40-wk weight maintenance phase. The subjects were divided into four groups according to their beta3AR and UCP-1 genotype: no mutation (control; n=37), only Trp64Arg mutation in the beta3AR gene (n=12), only A-->G mutation in the UCP-1 gene (n=23), and both mutations (n=5). Subjects with both mutations had a lower weight reduction during VLCD than the controls [-10.5+/-0.6 (+/-SEM) vs. -14.0+/-0.5 kg; P=0.051, by ANOVA]. During the maintenance phase, weight in subjects with both mutations increased by 5.8+/-1.5 kg, but remained unchanged in the controls (-0.5+/-0.8 kg; P=0.041). The changes in weight in subjects with only one of the mutation were close to the results in the controls. Resting energy expenditure, adjusted for fat mass, fat-free mass, and maximal aerobic power, did not change differently between the groups throughout the study. The results suggest that a combination of the Trp64Arg mutation in the beta3AR and the A-->G mutation in the UCP-1 genes may be associated with faster weight gain after a VLCD.

Adult↗

PubMed1998

Identification of new sequence variants in the leptin gene.

The leptin gene (LEP) has been linked to extreme obesity. However, no common obesity-related gene variants have been found to exist in the LEP. The present study was designed to investigate the LEP for variants by screening both the putative promoter and the coding region of this gene in obese Finnish subjects (n = 200; body mass index, > 27 kg/m2). PCR-amplified DNA samples were subjected to single strand conformation analysis. A G144A substitution in codon 48 and a G328A substitution in codon 110 were identified in two obese subjects, both of whom had very low serum leptin levels. A rare silent C538T polymorphism was detected 33 bp downstream of the translation stop codon (TGA). A common polymorphism A19G was identified in the untranslated exon 1. This polymorphism was not associated with traits of obesity; in agreement, the allele frequencies were similar between 64 normal weight and 141 obese Finns. In summary, this study failed to find a common gene variant in the LEP associated with obesity, but introduces 2 rare mutations associated with very low serum leptin concentrations in 2 obese subjects.

Adult↗

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

Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance.

OBJECTIVE: Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based study RESEARCH DESIGN AND METHODS: The population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information. CONCLUSIONS: The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.

Blood Glucose↗

PubMed1998

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus.

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.

Acarbose↗