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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 307 records · Page 17Linked to original sources

Effects of a very-low-calorie diet on metabolic control and cardiovascular risk factors in the treatment of obese non-insulin-dependent diabetics.

Ten obese non-insulin-dependent diabetics (six men, four women) with secondary drug failure were treated with a hypocaloric diet only (2100-3350 kJ/d) for 3 mo to assess the effects of weight reduction on metabolic control, energy production rate, and cardiovascular risk factors. During the 3 mo of follow-up the mean body weight decreased from 101.0 +/- 7.2 (means +/- SEM) to 87.2 +/- 5.5 kg (p less than 0.001). Basal energy production rate (kJ/min) decreased by 8.5%. Fasting blood glucose declined from 12.3 +/- 0.4 to 10.5 +/- 0.7 mmol/L (p less than 0.05) but mean diurnal glucose and glycosylated hemoglobin A1c did not change significantly. Serum total cholesterol was decreased at 2 wk but at 3 mo it did not differ significantly from the baseline value. A marked reduction was observed in serum triglycerides after 3 mo (4.57 +/- 1.0 vs 2.18 +/- 0.26 mmol/L, p = 0.012). The high-density lipoprotein (HDL) cholesterol increased after weight reduction (0.96 +/- 0.06 vs 1.11 +/- 0.05 mmol/L, p = 0.009). A significant decline was found in both systolic (152 +/- 6 vs 133 +/- 3 mm Hg, p = 0.004) and diastolic blood pressure (92 +/- 3 vs 81 +/- 3 mm Hg, p = 0.007). There was no evidence of linoleic acid deficiency after this diet.

Adult↗

Plasma insulin, serum lipids and lipoproteins in gall stone disease in non-insulin dependent diabetic subjects: a case control study.

Fasting insulin, lipids and lipoproteins were measured in 22 middle aged female non-insulin dependent diabetics with gall stone disease (cases) and in 22 non-insulin dependent diabetics without gall stone disease (controls). The groups were matched for sex, age, obesity, and fasting glucose concentrations. No differences were observed between the cases and controls in duration of diabetes, glycated haemoglobin A1, alcohol intake, smoking, use of cardiovascular drugs or a history of myocardial infarction. Diabetics with gall stone disease had higher fasting insulin concentrations (p less than 0.5), lower total (p less than 0.01) and low density lipoprotein cholesterol (p less than 0.01) and high density lipoprotein cholesterol (not statistically significant) concentrations than diabetics without gall stone disease. These changes in insulin, lipids and lipoproteins are similar to reported changes in non-diabetic subjects with gall stone disease. Therefore, they are characteristic for gall stone disease and not as such explanatory to an increased risk of gall stones in patients with non-insulin dependent diabetes.

Case-Control Studies↗

Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance.

Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 +/- 3 kg, mean +/- SEM) and six obese (94 +/- 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 +/- 0.2 to 4.4 +/- 0.2 dl/min in lean, P less than 0.01, and from 2.5 +/- 0.3 to 4.4 +/- 0.4 dl/min in obese subjects, P less than 0.01. The ED50 for insulin's effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P less than 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to lower glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin's hemodynamic action to increase blood flow to insulin sensitive tissues.

Adult↗

Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity.

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance.

Adult↗

Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans.

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity.

The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). We conclude that 1) the kinetics of in vivo insulin-mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin-mediated glucose extraction in skeletal muscle was 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose-transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake.

Adult↗

Prevalence of diabetes and impaired glucose tolerance in elderly subjects and their association with obesity and family history of diabetes.

The goal of this study was to investigate the prevalence of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in elderly subjects and their association with obesity, central obesity, and a family history of diabetes. A representative population sample of 1300 subjects (471 men, 829 women) aged 65-74 yr participated in the study. The participation rate was 71%. The prevalence rates of previously and newly diagnosed NIDDM and IGT, based on a history of diabetes and an oral glucose tolerance test, were 8.7, 7.0, and 17.8% in men and 11.7, 7.1, and 19.1% in women. Thus, 33.8% of men and 37.9% of women had abnormal glucose tolerance according to World Health Organization criteria. Obesity (body mass index greater than or equal to 27 kg/m2 in men and greater than or equal to 25 kg/m2 in women) and central obesity (waist-hip ratio greater than or equal to 0.98 in men and greater than or equal to 0.89 in women) doubled the prevalence of IGT or NIDDM. The combination of obesity and a family history of diabetes was associated with a more marked increase in the prevalence of IGT or NIDDM in men than in women. Simultaneous presence of obesity, central obesity, and a family history of diabetes was associated with a threefold increase in the prevalence of IGT or NIDDM (65.4 vs. 24.1% in men, 52.8 vs. 19.6% in women, P less than 0.001). The major risk factors for NIDDM, e.g., obesity, central fat distribution, and a family history of diabetes, explained 10% of the variance in 2-h glucose values in multiple regression analysis. In conclusion, the prevalence of IGT and NIDDM was high in elderly subjects. Although obesity, central fat distribution, and a family history of diabetes were significantly associated with the increased prevalence of IGT or NIDDM, they explained only a minor proportion of the variance in 2-h glucose values.

Age Factors↗

Longitudinal EEG spectral analysis in early stage of Alzheimer's disease.

Twenty-four patients with mild to moderate Alzheimer's disease (AD) were studied using quantitative spectral analysis of EEG at the time of the diagnosis and 1 year later. In 50% of the patients EEG spectra from the T6-O2 derivation were either normal or mildly abnormal at baseline and did not change at 1 year. In another half of the patients the mean quantitative EEG variables (the alpha and the delta power and the mean frequency) deteriorated significantly when baseline and 1 year values were compared. The patient groups with deteriorating and stable EEGs did not differ in age, sex, age at onset or duration of the disease or clinical severity at baseline or at 1 year. Dementia also progressed significantly in both subgroups of AD patients. We conclude that even if the mean values of quantitative EEG variables analysed from the T6-O2 derivation showed distinct slowing at the time of the AD diagnosis and further deterioration 1 year later, in 50% of these early AD cases there was no EEG alteration or worsening in 1 year follow-up, suggesting heterogeneity of the disease.

Aged↗

Serum lipids, lipoproteins, and apolipoproteins and the excessive occurrence of coronary heart disease in non-insulin-dependent diabetic patients.

Serum lipids, lipoproteins, and major apolipoproteins and their association with previous myocardial infarction were studied in patients with non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic subjects in East and West Finland in 1982-1984. NIDDM patients had higher age-adjusted serum triglyceride and apolipoprotein B levels and a higher apolipoprotein B/apolipoprotein A-I ratio, lower serum high density lipoprotein (HDL) cholesterol and apolipoprotein A-1 levels, and a lower HDL cholesterol/apolipoprotein A-1 ratio than nondiabetic subjects. With a few exceptions, these differences persisted after adjustment for body mass index, alcohol intake, physical activity, smoking, and hypertension, which suggests that the atherogenic serum lipoprotein pattern in NIDDM is an inherent feature of the disease. In general, the association of serum lipids, lipoproteins, and apolipoproteins with myocardial infarction was similar in nondiabetic subjects and NIDDM patients, although it was somewhat stronger in the diabetic subjects. A low serum HDL cholesterol/apolipoprotein A-1 ratio, which was closely linked to high serum triglyceride level, seemed to be more consistently related to myocardial infarction in NIDDM patients than in nondiabetic subjects. Serum lipids, lipoproteins, and apolipoproteins, either separately or in various combinations, could only to a small extent explain the higher prevalence of myocardial infarction in diabetic subjects compared with nondiabetic subjects when tested in multivariate analysis with other cardiovascular risk factors as background variables. The association between serum lipoproteins and myocardial infarction was largely similar in East and West Finland, two areas that differ markedly with respect to the occurrence of coronary heart disease.

Apolipoproteins↗

Essential hypertension and insulin resistance in non-insulin-dependent diabetes.

A recent study has shown that young, lean, hypertensive subjects are more insulin resistant than corresponding normotensive subjects. Whether this finding can also be demonstrated in the presence of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Therefore, the degree of insulin resistance was studied in 26 middle-aged hypertensive patients with NIDDM (11 men, 15 women) and 14 normotensive patients with NIDDM (eight men, six women) matched for age, metabolic control and the duration of diabetes, utilizing the glucose clamp technique. Non-obese NIDD patients (body mass index less than 27.0 kg m-2) with hypertension (n = 11) had significantly lower glucose disposal rates (GDRs) during the last 60 min of euglycaemic (5.5 mmol l-1) and hyperinsulinaemic (approximately 600 pmol l-1) clamp studies than NIDD patients without hypertension (n = 6) (782 +/- 94 vs. 1418 +/- 97 mumol m-2 min-1, P less than 0.05). In contrast, GDRs were similar in obese NIDD patients with (n = 15) and without (n = 8) hypertension (802 +/- 90 vs. 849 +/- 90 mumol m-2/min-1, respectively, P = NS). Basal hepatic glucose output, suppression of hepatic glucose production during hyperinsulinaemia and insulin secretion capacity did not differ between hypertensive and normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗

Cardiovascular mortality in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA), 500 men and 500 women, aged 40 years and over, together with a control population matched by age and sex were followed up with respect to cause-specific mortality over a 10-year period. The overall mortality was significantly higher in both men and women with RA than in the controls. A statistically significant increase in mortality from all cardiovascular diseases (p less than 0.001) and cardiac diseases (p = 0.004) was observed in men with RA but not in women with RA compared to corresponding controls. No difference in mortality from cerebrovascular diseases was observed between RA patients and controls.

Adult↗

Factors associated with fasting and postglucagon plasma C-peptide levels in middle-aged insulin-treated diabetic patients.

We studied fasting and postglucagon plasma C-peptide levels and factors associated with them in two representative studies of middle-aged insulin-treated diabetic patients whose diabetes had been diagnosed after the age of 30 yr. Altogether, 75 men and 79 women from East Finland and 83 men and 62 women from West Finland aged 45-64 yr were studied. Of these patients, 44.4% had undetectable fasting and 38.5% undetectable postglucagon C-peptide concentrations. The phi-coefficient expressing the concordance of fasting and postglucagon C-peptide concentrations in the classification of diabetic patients into nonresponders and responders was .75 in men and .91 in women. In multiple stepwise regression analyses, body mass index (BMI) and the period between diabetes diagnosis and the initiation of insulin treatment were positively and duration of diabetes inversely associated with fasting and postglucagon C-peptide levels in both sexes. We concluded that 1) insulin deficiency is not uncommon in middle-aged insulin-treated diabetic patients whose diabetes has been diagnosed after the age of 30 yr; 2) fasting C-peptide levels contain basically the same information as postglucagon C-peptide levels; and 3) a low BMI, a need for insulin treatment soon after the diagnosis of diabetes, and a long duration of diabetes are predictive of insulin deficiency.

C-Peptide↗

Endocrine patterns before and after examination stress in males and females.

Plasma levels of cortisol, adrenocorticotropin (ACTH), and growth hormone (GH), were determined by radioimmunoassay in medical students just before (Exp.1) plasma values of cortisol were higher than their control values in both sexes, statistically significantly, however, only in males. The difference of cortisol behavior between the sexes was not significant. The males' ACTH values were lower than their control levels, but there was no such difference in the females. Plasma levels and differences of growth hormone varied greatly in both sexes. After the examination (Exp.2) plasma values of cortisol were unaffected compared with their control values in both sexes. The ACTH values were lower than the control values in both sexes, significantly though only in the males. The GH values were higher than control values in the males but not in the females. The results are in line with previous observations suggesting that psychological stress is associated with slightly different hormonal effects in males and females.

Adrenocorticotropic Hormone↗

Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease.

Equilibrium radionuclide angiocardiography was performed on 19 men and 17 women with insulin-dependent diabetes mellitus (IDDM) and on 24 men and 15 women with noninsulin-dependent diabetes mellitus (NIDDM) and on 24 male and 24 female control subjects aged 46 to 67 years. All were without clinically evident cardiovascular disease. No significant differences were found in left ventricular (LV) ejection fraction at rest between men with IDDM (56 +/- 1%; mean +/- standard error of the mean) or NIDDM (58 +/- 1%) and control men (58 +/- 1%), whereas LV ejection fraction was higher in women with IDDM (63 +/- 1%; p less than 0.01) and NIDDM (64 +/- 2%; p less than 0.01) than in control women (58 +/- 1%). An abnormal LV ejection fraction response to dynamic exercise (an increase of less than 5% units or a decrease) was observed in 1 control man (4%), in 8 men with IDDM (42%, p less than 0.01) and in 10 men with NIDDM (42%, p less than 0.01). The respective figures were 4 (17%) for control women, 7 (44%, difference not significant) for women with IDDM and 10 (71%, p less than 0.01) for women with NIDDM. Abnormal LV ejection fraction response to exercise in diabetic patients was not related to the metabolic control of diabetes, presence of microangiopathy or abnormalities in the autonomic nervous function. Myocardial perfusion scintigraphy performed in 18 diabetic patients in whom LV ejection fraction decreased during exercise showed a reversible perfusion defect in only 5 (28%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Impairment of diastolic function in middle-aged type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients free of cardiovascular disease.

Left ventricular systolic and diastolic function was studied using systolic time intervals and echocardiography in 19 male and 17 female patients with Type 1 (insulin-dependent) diabetes, 24 male and 15 female patients with Type 2 (non-insulin-dependent) diabetes and 24 male and 24 female control subjects. The subjects for the present study were selected from a population based study in which 117 Type 1 and 510 Type 2 diabetic patients and 649 non-diabetic subjects were originally examined. After exclusions, none of the subjects had any evidence of coronary heart disease, hypertension or other diseases known to affect left ventricular function. There were no consistent differences in systolic time intervals or echocardiographic variables of systolic function between patients with Type 1 diabetes and non-diabetic control subjects; but patients with Type 2 diabetes showed an increased fractional shortening. Female patients with Type 2 diabetes showed an increased left ventricular mass not explicable by hypertension. Isovolumic relaxation period was longer in male (86 +/- 3 ms; mean +/- SEM) and female patients (84 +/- 6 ms) with Type 2 diabetes than in male (76 +/- 3 ms; p less than 0.05) and female (71 +/- 3 ms; p less than 0.05) control subjects. Peak diastolic filling rate was lower in female patients with Type 1 diabetes (12.8 +/- 0.8 cm/s, p less than 0.05) and in male (11.5 +/- 0.8 cm/s; p less than 0.01) and female patients (11.5 +/- 0.6 cm/s; p less than 0.001) with Type 2 diabetes as compared to male (14.4 +/- 0.7 cm/s) and female (14.9 +/- 0.5 cm/s) control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

Cholinergic deficit in Alzheimer's disease: a study based on CSF and autopsy data.

Cholinesterase (ChE) activity was measured as a possible marker of cholinergic neurotransmission of the brain in CSF of 93 patients with probable Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and of 29 control patients. ChE activity in CSF was decreased significantly in the AD/SDAT patients as compared to the controls. This reduction correlated significantly with the various measures of the severity of dementia. However, the reduction of ChE activity was only moderate (25-30%) even in patients with the most severe dementia and nonsignificant in patients with early symptoms of AD/SDAT. The significance of various confounding factors, which may interfere with CSF ChE measurements is discussed. Our findings seem to indicate that the deficiency of cholinergic neurons is not directly reflected in CSF and that the measurements of ChE activities in CSF are not helpful in diagnosing AD/SDAT. In the autopsy study the activities of cholineacetyltransferase (ChAT) and ChE were determined for ten brain areas of 20 AD/SDAT patients and of 14 controls. In AD/SDAT patients ChAT activity was profoundly decreased (50-85% decrease) in the cortical areas and hippocampus, but was unchanged or only mildly reduced in other subcortical brain areas. This study further confirms that the affection of cholinergic neurons is limited to projections from nucleus basalis to cortex and hippocampus, whereas other cholinergic neurons, like in striatum, seem to be relatively spared. In general, the activities of ChAT and ChE were lower in Alzheimer patients dying at younger age suggesting more severe disease process with these patients.

Aged↗