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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 271 records · Page 15Linked to original sources

Insulin resistance in familial and nonfamilial hypercholesterolemia.

High levels of very low density lipoprotein triglycerides and low levels of high density lipoprotein cholesterol have been found to be associated with insulin resistance measured by the euglycemic clamp technique. In contrast, the association of isolated hypercholesterolemia with insulin resistance has not been systematically studied. Therefore, we performed two separate studies designed to investigate the degree of insulin resistance in familial hypercholesterolemia (FH) (study 1) and nonfamilial hypercholesterolemia (non-FH) (study 2). Study 1 included eight young adults with FH and 13 corresponding control subjects. Fasting blood glucose, insulin, and C-peptide levels were similar in FH patients and control subjects during an oral glucose tolerance test. During the euglycemic hyperinsulinemic (1,200-1,300 pmol/l) clamp studies, FH patients and control subjects had similar rates of whole-body glucose uptake (73 +/- 6 versus 70 +/- 3 mumol/kg per minute, respectively; p = NS). Glucose oxidation, glucose nonoxidation, lipid oxidation, suppression of free fatty acid levels, and potassium disposal were similar in both groups. Study 2 included 25 middle-aged non-FH patients and 18 corresponding control subjects. Glucose, insulin, and C-peptide responses in an oral glucose tolerance test were similar in both groups. During the euglycemic hyperglycemic clamp studies, non-FH patients and control subjects had similar rates of whole-body glucose uptake (61 +/- 3 versus 58 +/- 3 mumol/kg per minute, p = NS). In addition, glucose oxidation, glucose nonoxidation, lipid oxidation, and suppression of free fatty acid levels as well as potassium disposal were similar in non-FH patients and control subjects. We conclude that FH and non-FH are not insulin-resistant states.

Blood Glucose↗

Obese men with type IIB hyperlipidemia are insulin resistant.

By using the euglycemic clamp technique and indirect calorimetry, we determined the degree of insulin resistance in 12 obese (body mass index > 27.0 kg/m2), normotensive patients with type IIB hyperlipidemia (HLIIB) (total cholesterol > or = 6.5 mmol/L and total triglycerides > or = 2.0 mmol/L) and 17 control subjects (total cholesterol < or = 6.1 mmol/L and total triglycerides < 1.8 mmol/L) who were carefully matched for sex, age, and obesity. Fasting plasma insulin was higher in HLIIB patients than in control subjects (18.4 +/- 4.6 versus 8.9 +/- 1.2 mU/L, respectively; P = .010). The rates of whole-body glucose uptake were significantly lower in HLIIB patients than in control subjects during the last hour of the clamp (42.2 +/- 3.9 versus 54.6 +/- 2.8 mumol/kg per minute, respectively; P = .013). Glucose oxidation during the last 30 minutes of the euglycemic clamp was lower in HLIIB patients than in control subjects (14.6 +/- 0.9 versus 19.0 +/- 1.3 mumol/kg per minute, respectively; P = .017). Nonoxidative glucose disposal during the last 30 minutes of the euglycemic clamp was also lower in HLIIB patients than in control subjects, but the difference was not statistically significant (27.6 +/- 3.3 versus 35.8 +/- 2.8 mumol/kg per minute, respectively; P = .069). Lipid oxidation during the clamp was completely suppressed in control subjects (-0.24 +/- 0.44 mumol/kg per minute) but was significantly less suppressed in the HLIIB patients (0.94 +/- 0.29 mumol/kg per minute, P = .024).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes.

BACKGROUND: The aim of this study was to investigate the association of lipoprotein fractions with the future risk of coronary heart disease (CHD) in patients with non-insulin-dependent diabetes (NIDDM). METHODS AND RESULTS: At baseline, lipoprotein fractions were determined in 313 diabetic patients with NIDDM (153 men and 160 women), and these patients were followed up for 7 years with respect to CHD events (CHD death or all CHD events including CHD death or nonfatal myocardial infarction). Altogether, 56 NIDDM patients (28 men and 28 women) died from CHD and 25 had a nonfatal myocardial infarction (17 men and 8 women) during the follow-up. NIDDM patients having these CHD events during the follow-up had higher levels of total and very-low-density lipoprotein (VLDL) triglycerides and VLDL cholesterol and lower levels of high-density lipoprotein (HDL) and HDL2 cholesterol than those without CHD events. The risk for CHD death was fourfold and for all CHD events, twofold higher among diabetics with low HDL cholesterol (< 0.9 mmol/L) than among diabetics with HDL cholesterol > or = 0.9 mmol/L. High triglyceride level (> 2.3 mmol/L) was associated with a twofold increase in the risk of CHD events. In multiple logistic regression analyses, HDL was inversely associated with CHD events and VLDL triglycerides with CHD events in NIDDM patients with low HDL cholesterol level (< or = 1.12 mmol/L). CONCLUSIONS: Our 7-year follow-up study gives evidence that low HDL and HDL2 cholesterol, high VLDL cholesterol, and high total and VLDL triglycerides are powerful risk indicators for CHD events in patients with NIDDM:

Cholesterol↗

Essential hypertension and cognitive function. The role of hyperinsulinemia.

The relation between hypertension and cognitive function is not well established. Therefore, we examined cognitive function in a random sample of 744 nondiabetic elderly inhabitants of Kuopio, East Finland. Five brief neuropsychological tests known to be sensitive to cognitive impairment due to dementia--the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT), the Buschke Selective Reminding Test (BSR), Russell's Adaptation of the Visual Reproduction Test (HVR), and the Verbal Fluency Test (VFT)--were used to evaluate cognitive function. The performance of the hypertensive group (n = 378) was impaired in almost all test items compared with that of the normotensive group (n = 366), but the difference between these two groups was statistically significant in 5 of 19 test items only. Moreover, within the hypertensive group, hyperinsulinemic (fasting plasma insulin > 17.9 mU/L) hypertensive subjects (n = 57) scored worse than normoinsulinemic hypertensive subjects (n = 321) in 16 of 19 test items and worse than the normotensive subjects in the same 16 of 19 test items. The difference between the hyperinsulinemic hypertensive and normotensive groups was significant in 11 test items that reflected complex cognitive function such as calculation, language, semantic memory, and problem solving. This difference in neuropsychological tests among the three study groups (normotensive, normoinsulinemic hypertensive, and hyperinsulinemic hypertensive subjects) persisted after adjustment for fasting plasma glucose, age, sex, and education in 3 test items measuring calculation, copying, and semantic memory. Thus, essential hypertension in the elderly is associated with an impairment in complex cognitive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Lower-extremity amputations in diabetic and nondiabetic patients. A population-based study in eastern Finland.

OBJECTIVE: To study the incidence of LEAs attributable to PVD in diabetic and nondiabetic patients. The age at first amputation, the level of amputation, the number of reamputations, and survival after amputation also were examined in the study populations. RESEARCH DESIGN AND METHODS: This retrospective study was based on a population of 253,000 inhabitants in eastern Finland. All patients with their first LEA performed during the period from 1 January 1978 to 31 December 1984 were identified from the registers of operation theaters in the study area. Furthermore, patient records and death certificates were reviewed. Amputations attributable to causes other than evident atherosclerotic vascular disease were excluded. RESULTS: Altogether, 477 patients (85 diabetic men, 127 nondiabetic men, 169 diabetic women, and 96 nondiabetic women) were identified. The overall LEA rate was 26.9/100,000 per yr, and the incidence increased strongly with age in both diabetic and nondiabetic patients. The age-adjusted amputation incidence per yr was 349.1/100,000 for diabetic men, 33.9/100,000 for nondiabetic men, 239.4/100,000 for diabetic women, and 17.2/100,000 for nondiabetic women. The proportion of peripheral (toe, leg) amputations was markedly higher in diabetic patients who also tended to have more reamputations during the follow-up than did nondiabetic subjects. The diabetic status per se was a statistically significant risk factor for mortality in women, but not in men. CONCLUSIONS: Diabetic men and women had a 10.3- and 13.8-fold higher risk, respectively, for LEA.

Adult↗

Voluntary eye movement tests in patients with insulin-dependent diabetes mellitus.

Eye movement tests (saccade tests: reaction time, peak velocities and accuracy, and the eye tracking test) were studied in 53 insulin-dependent diabetic (IDDM) patients and 42 randomly selected non-diabetic control subjects, aged between 20 and 40 years. All subjects had central visual acuity of at least 0.1 in one eye, and none had ophthalmoplegia. The reaction time was longer and the accuracy decreased in the saccade test in diabetic patients as compared to control subjects. Peak velocities tended to be slower in diabetic patients, but no significant differences between diabetic and non-diabetic subjects were observed. The maximum eye movement velocities were reduced at all target velocities in diabetic patients as compared to control subjects. These findings can be explained on the basis of many potential disturbances in the central nervous system. Only the duration of diabetes had a clear association with maximum smooth pursuit eye movement velocities in the eye tracking test. Microvascular complications (retinopathy, nephropathy), autonomic neuropathy or metabolic control (high fasting blood glucose and glycated hemoglobin A1c) had no clear association with the results of eye movement tests. In conclusion, insulin dependent diabetes mellitus deteriorates the visuomotor responses.

Adult↗

Increased urinary polyamine excretion after starting a very low calorie diet.

Urinary polyamine excretion has been suggested to reflect hypermetabolism or catabolism in different illnesses. In the present study, the excretion of urinary polyamines was examined in 12 obese subjects (3 men, 9 women aged 32-55 y, body mass index 33.3-64.7 kg m-2) before and during a very low calorie diet (the total calorie intake 2100-3350 kJ). In addition, nitrogen balance, basal energy expenditure (BEE) and serum thyroid hormone levels were examined. During the first week on a very low calorie diet (VLCD) the mean body weight declined from 121.8 +/- 27.3 to 117.4 +/- 26.2 kg (mean +/- SD, p < 0.001), and after 12 weeks of treatment body weight was 106.6 +/- 24.6 kg. Immediate reduction of BEE from 1.44 +/- 0.24 to 1.34 +/- 0.24 kcal min-1 (p < 0.001) was found within the first week of therapy and BEE measured on weight-maintaining diet remained lower at 12 weeks (1.25 +/- 0.27 kcal min-1, p < 0.01). Serum free T3 decreased and reverse T3 increased significantly after starting VLCD. Nitrogen balance remained negative during the first 2 weeks on VLCD. A significant increase in total (38%), and in N1-acetyl- and N8-acetylspermidine excretions in the urine (40% and 27%, respectively, p < 0.05) was found during the first week, but later on the levels were not significantly different from the baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Gastrointestinal symptoms in middle-aged diabetic patients.

Occurrence of gastrointestinal symptoms was investigated in a questionnaire-based survey of 89 randomly selected patients with insulin-dependent diabetes mellitus, 481 patients with noninsulin-dependent diabetes mellitus, and 635 nondiabetic control subjects. The prevalences of upper gastrointestinal symptoms, abdominal pain, diarrhea, and constipation were similar in diabetic patients and control subjects. Women with noninsulin-dependent diabetes mellitus had a significantly higher and women with insulin-dependent diabetes mellitus a significantly lower prevalence of gallstone disease than control women (29%, 5%, and 19%, respectively). We conclude that the occurrence and spectrum of gastrointestinal symptoms in middle-aged subjects with insulin- and noninsulin-dependent diabetes mellitus do not differ from those of the general population.

Cholelithiasis↗

Tympanometry in patients with insulin-dependent diabetes mellitus.

Tympanograms were studied in 53 patients with insulin-dependent diabetes mellitus (IDDM) and 42 randomly selected non-diabetic control subjects, aged between 20 and 40 years, using the Madsen Model ZO 73 Impedance Bridge. Subjects with abnormal tympanic membrane, conductive hearing loss and known reason for hearing impairment (e.g. noise damage) were excluded from the study. The mean tympanogram amplitudes in diabetic patients were significantly lower in both ears than those of control subjects. The duration of diabetes and microvascular complications (nephropathy and retinopathy) were associated with decreased amplitudes. These findings indicate that decreased tympanogram amplitudes in patients with IDDM are probably caused by diabetes of long duration and the microvascular complications associated with it.

Acoustic Impedance Tests↗

Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group.

Osteolytic lesions and pathological fractures are common in multiple myeloma. Because clodronate inhibits osteoclastic resorption, we did a randomised, controlled trial in 350 patients from 23 hospitals. All patients received standard melphalan-prednisolone, and were randomised to receive clodronate 2.4 g daily or placebo for 24 months. The proportion of patients with progression of osteolytic bone lesions was twice as high in the placebo group (n = 168 at baseline) than in the clodronate group (n = 168 at baseline) in an intention-to-treat analysis (24 vs 12%, p = 0.026). Progression of vertebral fractures was lower in the clodronate group, but the difference was not significant (30 vs 40%). Serum calcium and urinary calcium excretion decreased significantly in both groups, but the changes were greater in the clodronate group. The percentage of patients feeling no pain increased more in the clodronate group (from 24 to 54%, p < 0.001) than in the placebo group (from 29 to 44%, p < 0.01). Side-effects were similar in both groups. We conclude that clodronate is an effective and safe adjunct in the management of multiple myeloma. The drug delays osteolytic bone lesions, reduces the degree of hypercalcaemia and hypercalciuria, and decreases pain.

Aged↗

Prevalence of isthmic lumbar spondylolisthesis in middle-aged subjects from eastern and western Finland.

Isthmic spondylolisthesis of the lumbosacral spine is a common radiologic finding in patients with low back pain, but its prevalence in unselected populations is poorly known. We examined X-ray pictures of the lumbosacral region of 1147 randomly selected 45-64-yr-old subjects living in eastern or western Finland. Of them, 69 subjects were found to have isthmic spondylolisthesis. The finding was more common in men (7.7%) than in women (4.6%; p = 0.026). The prevalence of spondylolisthesis was not age-related; it was higher in women with an occupation causing a high back load than in those with a low load occupation (p = 0.049), but this difference was not seen in men. The prevalence of spondylolisthesis tended to be higher in women with multiple pregnancies than in those with less than or equal to 2 pregnancies (p = 0.074). Women from eastern Finland had a higher prevalence of spondylolisthesis (7.2%) than those from western Finland (2.6%; p = 0.007), whereas no such difference was seen in men. The difference in women may partly be explained by factors causing loading of the low back, i.e. heavier work and a higher number of pregnancies.

Female↗

Effects of bezafibrate on insulin sensitivity and glucose tolerance in subjects with combined hyperlipidemia.

To investigate whether the lowering of triglyceride levels has beneficial effects on glucose metabolism, we studied 13 nondiabetic men with combined hyperlipidemia (phenotype IIB) before and after 2 months of treatment with a slow-release formulation of bezafibrate (400 mg daily). The rates of whole body glucose disposal were quantitated by the euglycemic hyperinsulinemic clamp technique (insulin infusion rate of 80 mU/m2/min). In an oral glucose tolerance test, fasting glucose level decreased slightly (5.0 +/- 0.2 versus 4.8 +/- 0.2 mmol/L; p < 0.05) during bezafibrate treatment. Glucose and insulin levels after an oral glucose load remained unchanged. Rates of whole body glucose disposal did not change during bezafibrate treatment (39.5 +/- 3.3 mumol/kg/min before treatment versus 40.6 +/- 2.7 mumol/kg/min after treatment; difference not significant). Basal hepatic glucose output also remained unchanged (8.2 +/- 0.2 mumol/kg/min before treatment versus 8.3 +/- 0.2 mumol/kg/min after treatment; difference not significant). Our findings show that bezafibrate has a triglyceride-lowering effect without any significant influence on insulin sensitivity.

Bezafibrate↗

Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels.

Altogether twenty-six elderly subjects (aged 65-74 years) with persistent impaired glucose tolerance (World Health Organization (1985) criteria) identified in a population-based study, were randomly treated either with chromium-rich yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n 13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11 (SE 0.02) micrograms/d). No significant change was observed in the oral glucose tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3 (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE 0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v. 4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v. 6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein A1 and B levels remained unchanged, and no improvement was seen in serum total cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4) v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein-cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1) v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4) v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for the placebo group). The present results indicate that Cr supplementation does not improve glucose tolerance or serum lipid levels in elderly subjects with stable impaired glucose tolerance.

Aged↗

Autonomic nervous function and its relationship to cardiac performance in middle-aged diabetic patients without clinically evident cardiovascular disease.

Autonomic nervous function was evaluated in 36 patients with insulin-dependent diabetes mellitus (IDDM), 39 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 48 control subjects, all without clinically evident cardiovascular disease. Valsalva ratio and heart rate variation during deep breathing were lower in both diabetic groups than in the control group. Autonomic nervous function score (ANFS) was more abnormal in patients with IDDM than in control subjects, but was not significantly increased in patients with NIDDM. There was a negative correlation between ANFS and left ventricular diastolic filling evaluated by echocardiography or peak heart rate during exercise in both diabetic groups. There were no correlations between ANFS and left ventricular systolic function at rest or during exercise in any of the groups. In conclusion, autonomic nervous function was abnormal in middle-aged diabetic patients, and it was associated with impaired left ventricular diastolic filling at rest and decreased heart rate response to exercise, but not with left ventricular systolic function.

Analysis of Variance↗

Effects of epinephrine on insulin-mediated glucose uptake in whole body and leg muscle in humans: role of blood flow.

In vivo insulin-mediated glucose uptake (IMGU) occurs chiefly in skeletal muscle, where it is determined by the product of arteriovenous glucose difference (delta AVG) and blood flow (BF) rate into muscle. Epinephrine (Epi) reduces the rate of IMGU in whole body. To examine whether this is due to a reduction in delta AVG across or BF into skeletal muscle we constructed insulin dose-response curves for whole body IMGU and leg muscle IMGU- using euglycemic clamp ((+)[3-3H]glucose infusion) and leg balance techniques during insulin infusions ranging from 10 to 1,200 mU.m-2.min-1. We studied six subjects [wt 70 +/- 2 (SE) kg] during an Epi infusion at a single rate of 0.002 mg.kg-1.min-1 and six subjects (70 +/- 3 kg) during a saline infusion alone. Maximum whole body glucose uptake (WBGU) was similar during Epi and saline infusions [71.4 vs. 73.6 mmol.kg-1.min-1, P = not significant (NS)]. Compared with saline, maximum delta AVG was decreased during Epi infusion (1.04 vs. 1.31 mM, P less than 0.01). Compared with saline alone maximum leg BF was increased (5.3 vs. 4.3 dl/min, P less than 0.01) during Epi infusion. Thus maximum leg glucose uptake (LGU) was similar (696 vs. 821 pmol.leg-1.min-1, P = NS) during infusion of Epi and saline, respectively. Half-maximal effective dose for insulin's effect to stimulate WBGU, delta AVG, BF, and LGU was increased two- to threefold during Epi vs. saline infusions (P less than 0.01 for all values).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation↗

Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes.

Coronary heart disease risk factor levels were studied in 184 first-degree relatives (sisters and brothers) of non-insulin-dependent diabetic subjects (124 relatives with normoglycemia, 34 relatives with impaired glucose tolerance [IGT], and 26 relatives with non-insulin-dependent diabetes mellitus [NIDDM]) and in 215 relatives of nondiabetic subjects (194 relatives with normoglycemia and 21 relatives with IGT). Subjects with IGT exhibited the highest insulin responses to an oral glucose load. Systolic blood pressure was significantly higher; serum high density lipoprotein cholesterol level was significantly lower; and total, low density lipoprotein, and very low density lipoprotein triglyceride levels were higher in the relatives with a family history of diabetes who had IGT or NIDDM than in the normoglycemic relatives without a family history of diabetes. These abnormal changes were not seen in normoglycemic relatives or relatives with IGT who had no family history of NIDDM. Thus, in relatives of diabetics, abnormal glucose tolerance seems to induce changes in cardiovascular heart disease risk factor levels that are similar to those observed in NIDDM. Therefore, a family history of diabetes adds substantially to the risk for atherosclerosis, particularly in subjects with IGT.

Apolipoproteins↗

European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke.

BACKGROUND AND PURPOSE: The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction. METHODS: The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients. RESULTS: The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects. CONCLUSIONS: The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result.

Aged↗