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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 325 records · Page 18Linked to original sources

Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease.

Coronary heart disease in insulin-dependent (IDDM) and in non-insulin-dependent diabetes (NIDDM) is associated with lipid and lipoprotein changes favouring atherosclerosis. Whether lipid and lipoprotein abnormalities are associated also with peripheral vascular disease in both types of diabetes is largely unknown. Therefore, we studied lipid and lipoprotein levels and their association with claudication in a representative sample of diabetic and non-diabetic subjects in East Finland. Altogether 87 subjects had IDDM (43 men, 44 women), 264 subjects NIDDM (126 men, 138 women) and 120 subjects were non-diabetic controls (63 men, 57 women). Patients with IDDM had an increased level of HDL and HDL2-cholesterol and patients with NIDDM a decreased level of HDL and HDL2-cholesterol and an increased level of total, LDL and VLDL triglycerides than did non-diabetic subjects. Analyses in both types of diabetes by claudication status revealed that total and LDL-cholesterol and total and VLDL triglycerides tended to be higher and HDL and HDL2-cholesterol lower in those having claudication as compared to those without a claudication symptom. Similarly, total cholesterol/HDL-cholesterol ratio and LDL-cholesterol/HDL-cholesterol ratio were also more atherogenic in patients with claudication than in those without claudication. In conclusion, our results indicate that in both types of diabetes peripheral vascular disease is associated with lipid and lipoprotein abnormalities favouring atherosclerosis.

Body Weight↗

A post-mortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease.

Involvement of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) was studied in 20 histologically confirmed AD/SDAT cases by comparing these with 14 control patients. Concentrations of noradrenaline (NA) were decreased significantly in the frontal cortex, temporal cortex, hippocampus and putamen in AD/SDAT. Serotonin (5-HT) levels were significantly lowered in the hippocampal cortex, hippocampus, caudate nucleus and putamen and the concentrations of 5-HIAA, a metabolite of 5-HT, were reduced in 3 cortical areas, thalamus and putamen in patients with AD/SDAT. Furthermore, 5-HIAA/5-HT ratios were in general slightly lower in AD/SDAT reaching significance in the temporal and hippocampal cortex. Glutamic acid decarboxylase (GAD) enzyme activity was not changed significantly in AD/SDAT although patients without evidence of premortem hypoxia and hypovolemia showed a consistent trend for increased GAD activity in the thalamus, striatum and substantia nigra. These findings further confirm the involvement of NA and 5-HT neuronal systems in AD/SDAT. The damage of 5-HT neurons seemed to be more generalized and more severe than that of NA neurons. The possible clinical relevance of these findings is briefly discussed and the need for critical evaluations of the behavioral effects related to these abnormalities described in patients with AD/SDAT is emphasized.

Aged↗

Effects of hypocaloric diet and insulin therapy on metabolic control and mechanisms of hyperglycemia in obese non-insulin-dependent diabetic subjects.

We studied the effects of hypocaloric diet (500 kcal/d) and insulin therapy in 15 obese (body mass index greater than 30.0 kg/m2) non-insulin-dependent diabetic patients with secondary drug failure and poor metabolic control. The patients were randomly allocated either to hypocaloric diet (n = 8) or to insulin treatment (n = 7). After 2 weeks of treatment there was a significant improvement in the fasting blood glucose, in the mean diurnal glucose, in glucosuria, and in glucose response to a 75-g oral glucose load in both groups. No change in insulin secretion was seen in either group. Glucose disposal rates (GDR) improved significantly both in the diet-treated group (from 2.34 +/- 0.15 to 4.01 +/- 0.40 mg/kg/min, P less than .01) and in the insulin-treated group (from 2.46 +/- 0.33 to 2.77 +/- 0.29 mg/kg/min, P less than .01). The improvement was greater in the diet-treated group (71%) than in the insulin-treated group (13%, P less than .05). The increase of GDR in the diet-treated group was due to an increase of nonoxidative GDR (from 1.18 +/- 0.17 to 2.98 +/- 0.39 mg/kg/min, P less than .001) as assessed by indirect calorimetry. In the insulin-treated group there was a small increase both in oxidative and nonoxidative GDR, but the changes were not statistically significant. Hepatic glucose output (HGO) in a postabsorptive state decreased significantly both in the diet-treated group (from 2.49 +/- 0.15 to 2.04 +/- 0.10 mg/kg/min, P less than .01) and in the insulin-treated group (from 2.63 +/- 0.23 to 2.05 +/- 0.12 mg/kg/min, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stopping insulin treatment in middle-aged diabetic patients with high postglucagon plasma C-peptide. Effect on glycaemic control, serum lipids and lipoproteins.

We studied the successfulness of stopping insulin treatment in middle-aged diabetic patients aged 45-64 with a high postglucagon C-peptide level and the effects of this change on glycaemic control, serum lipids and lipoproteins. Insulin treatment was successfully stopped in 15 of our 22 patients who satisfied the inclusion criteria for the study and were selected on the basis of a computer file including practically all diabetic patients treated with insulin in the Kuopio University Central Hospital region (population base 250,000 inhabitants). Insulin therapy was restarted in seven patients during the first 3 months after discharge. During the following 9 months insulin therapy was restarted in another three patients so that after a 1-year follow-up period half of the diabetic patients whose insulin therapy was stopped had been switched back to insulin. Insulin therapy was seldom successfully stopped if the postglucagon C-peptide value was under the limit of 1.0 nmol/l. Glycaemic control did not change during the follow-up, although there was a significant weight loss in diabetic patients. No changes were observed in serum lipids or lipoproteins with the exception of LDL cholesterol, which showed a significant reduction during the 3-month follow-up. In conclusion, insulin therapy can often be successfully stopped in patients with postglucagon C-peptide over the limit of 1.0 nmol/l without worsening of glycaemic control and without unfavourable changes in serum lipid and lipoprotein levels.

C-Peptide↗

Atherosclerotic vascular disease and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects in Finland.

A cross-sectional study on the prevalence of atherosclerotic vascular disease (ASVD) and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects was carried out from 1982 to 1984 in East Finland (Kuopio) and West Finland (Turku), two areas known to differ markedly in prevalence of ASVD in the nondiabetic population. A total of 510 diabetic and 649 nondiabetic subjects aged 45-64 yr were examined in East Finland and 549 diabetic and 724 nondiabetic subjects of the same age in West Finland. In both areas and in both sexes the prevalence of coronary heart disease (CHD), stroke, and intermittent claudication was higher in diabetic than in nondiabetic subjects. Both in diabetic and nondiabetic subjects the prevalence of ASVD was higher in East Finland than in West Finland. In men, the East-West difference in the prevalence of symptomatic CHD and claudication was greater in diabetic than in nondiabetic subjects. In both areas and in both sexes the serum lipid pattern was more atherogenic and hypertension was more frequent in diabetic than in nondiabetic subjects. In both diabetic and nondiabetic subjects, serum total-cholesterol level was somewhat higher and hypertension was more frequent in East Finland than in West Finland. The East-West difference in serum total-cholesterol was greater in diabetic than in nondiabetic subjects. In multiple logistic analyses including cardiovascular risk factors, diabetes status, and area of residence, residence in East Finland was found to be, in addition to diabetes, a strong independent factor associated with CHD, particularly in men.

Arteriosclerosis↗

Improvement of left ventricular function after starting insulin treatment in patients with non-insulin-dependent diabetes.

Left ventricular function was evaluated noninvasively before and three months after starting insulin treatment in nine patients (mean age 61.8 years, range 51-68 years) with non-insulin dependent diabetes showing an impaired insulin secretion capacity. After starting insulin treatment, fasting blood glucose decreased from 12.9 +/- 0.5 mmol/l (mean +/- SEM) to 9.8 +/- 1.2 mmol/l (p = 0.03), but the decrease of glycosylated haemoglobin Alc was not significant (9.0 +/- 0.4% vs. 8.3 +/- 0.6%). On systolic time intervals, PEP/LVET ratio improved from 0.44 +/- 0.03 to 0.37 +/- 0.02 (p = 0.03). On M-mode echocardiography, E-F slope became steeper (89 +/- 6 mm/sec vs. 103 +/- 8 mm/sec; p = 0.01) but no significant changes were observed in other variables reflecting diastolic or systolic function. On equilibrium radionuclide angiocardiography, the left ventricular ejection fraction at rest was similar before and after starting insulin treatment (48.6 +/- 3.2% vs. 49.2 +/- 2.8%) but during peak exercise the left ventricular ejection fraction improved significantly (51.0 +/- 5.3% vs. 59.9 +/- 4.7%; p = 0.02). The change of PEP/LVET ratio correlated significantly with the changes of blood glucose and glycosylated haemoglobin Alc levels, but the correlation between these metabolic variables and the change of left ventricular ejection fraction during exercise did not reach statistical significance. In conclusion, the left ventricular function improved concomitantly with improved metabolic control after starting insulin treatment in middle-aged patients with non-insulin-dependent diabetes having an impairment in insulin secretion capacity. This finding suggests that metabolic factors are involved in the left ventricular dysfunction observed in diabetes.

Blood Glucose↗

Decreased muscarinic receptor binding in cerebral cortex and hippocampus in Alzheimer's disease.

Muscarinic (cholinergic) receptor binding sites (MRB) were studied by determining the 3H-QNB binding in four cortical areas and hippocampus of 20 histologically confirmed Alzheimer patients and comparing these with corresponding controls. Alzheimer patients dying at younger age (less than or equal to 80) with profound decrease in choline-acetyltransferase activity (by 61-85%) and without any, possibly MRB modifying, drug treatment showed 30% decrease in MRB in the frontal cortex (p less than 0.05), 28% in the temporal cortex (p less than 0.05) and 37% in the hippocampus (p less than 0.01). These findings further suggest that muscarinic receptors are affected in Alzheimer's disease, at least in advanced state of the disease.

Aged↗

Diseases and drugs causing prolongation of the QT interval.

The prolonged QT interval and its association with diseases and drugs was studied on the basis of computerized electrocardiograms recorded in the region of the Kuopio University Central Hospital, East Finland. Altogether, 33,655 persons in whom at least 1 electrocardiogram was recorded from 1975 to 1983 were found. The study population consisted of 183 persons with prolonged QT intervals (at least 470 ms) and 187 with normal QTc intervals (440 ms or less), aged 45 to 64 years. These subjects were selected from 14,990 persons eligible. No difference in the prevalence of diseases affecting the QTc interval was found between those with long QTc intervals and those with normal QTc intervals. No difference between the groups was found in use of quinidine, procainamide or disopyramide. When the comparison was made on the basis of all group 1A antiarrhythmic drugs (quinidine, procainamide and disopyramide combined), persons with prolonged QTc intervals used these drugs more often than did those with normal QTc intervals (p = 0.031). Use of sotalol was significantly more common (p less than 0.001) in subjects with long QTc intervals. The mortality rate was also higher in persons with prolonged QTc interval (p less than 0.001), and most deaths during follow-up were due to coronary artery disease.

Anti-Arrhythmia Agents↗

Diabetes and atherosclerosis: an epidemiologic view.

Diabetes is associated with changes in plasma lipids and lipoproteins into atherogenic direction. In IDDM these changes are small or absent if good metabolic control can be maintained. Diabetic nephropathy is, however, associated with the appearance of dyslipoproteinemia. In NIDDM plasma total and VLDL triglyceride levels are elevated, and HDL-cholesterol level is decreased, and this pattern of dyslipoproteinemia does not always respond to improved control of hyperglycemia. Abnormalities of lipoprotein metabolism, not reflected in conventional plasma lipid and lipoprotein level measurements, and glucosylation of lipoproteins and resulting alterations in lipoprotein catabolism may be of importance in the enhanced atherogenesis in diabetes. Both IDDM and NIDDM are associated with an increased frequency of hypertension, but the underlying mechanisms appear to be different. In IDDM hypertension is usually associated with the development of diabetic nephropathy and thus with a long duration of the disease. In NIDDM hypertension is often present already at the time of diagnosis, and also in IGT, the precursor stage of NIDDM, the prevalence of hypertension is already increased. Obesity explains only in part the high prevalence of hypertension in patients with NIDDM. Diabetes is known to be associated with multiple abnormalities in hemostatic factors and, although these abnormalities may contribute importantly to the increased risk of ASVD in diabetic patients, information about their real role is scanty and conflicting. The impact of general major risk factors for ASVD, elevated plasma cholesterol, elevated blood pressure, and smoking, on the risk of ASVD appears to be similar in diabetics and nondiabetics. Only a relatively small proportion of the excessive occurrence of ASVD in diabetics can, however, be explained by the effects of diabetes on the levels of general risk factors for ASVD. This proportion mediated through the effects of diabetes on risk factors is larger in female diabetics than in male diabetics. The major proportion of the excess of ASVD in diabetics remains, however, unexplained and must be due to effects of diabetes itself through mechanisms that are incompletely understood.

Arteriosclerosis↗

Relationship between postheparin plasma lipases and high-density lipoprotein cholesterol in different types of diabetes.

We measured serum lipids, lipoproteins and post-heparin plasma lipases, lipoprotein lipase and hepatic lipase, in 12 female patients with Type 1 (insulin-dependent) diabetes (postglucagon C-peptide undetectable), in 11 female insulin-treated patients with Type 2 (non-insulin-dependent) diabetes (postglucagon C-peptide greater than 0.60 nmol/l) and in 16 non-diabetic female control subjects. These three groups of subjects were similar with respect to age and obesity. Insulin dose was similar in patients with Type 1 and with Type 2 diabetes. HDL and HDL2 cholesterol were lower in patients with Type 2 diabetes than in non-diabetic control subjects (p less than 0.05) but did not differ between patients with Type 1 diabetes and non-diabetic control subjects. No difference in lipoprotein lipase activity was seen between the groups. The highest levels of lipoprotein lipase and hepatic lipase activities were observed in patients with Type 2 diabetes. Lipoprotein lipase activity correlated significantly with HDL cholesterol in patients with Type 1 diabetes (p less than 0.01) and in patients with Type 2 diabetes (p less than 0.001) but not in control subjects. Hepatic lipase activity did not correlate significantly with HDL cholesterol in any of the groups. In conclusion, postheparin plasma lipoprotein lipase and hepatic lipase activities do not seem to explain the difference in HDL cholesterol concentration between patients with Type 1 and Type 2 diabetes.

Apoproteins↗

Association of serum lipids and lipoproteins with plasma C-peptide concentration in non-insulin-dependent diabetic and non-diabetic subjects.

Serum lipids and lipoproteins were studied in 149 non-insulin-dependent diabetic subjects treated with diet or oral drugs (75 men, 74 women) and in 101 nondiabetic control subjects (49 men, 52 women) in relation to endogenous insulin secretion capacity measured by plasma C-peptide response to intravenous glucagon. Serum HDL- and HDL2-cholesterol concentrations were lower and VLDL-cholesterol and total and VLDL-triglyceride concentrations higher in subjects with high C-peptide response (above the median) than in subjects with low C-peptide response (lower or equal to median) both in diabetic and control subjects of both sexes. Adjustment for the effect of obesity abolished these differences in serum lipids and lipoproteins in diabetic subjects but not in control subjects. This may indicate that obesity has stronger influence on serum lipids in diabetic subjects than in nondiabetic subjects.

Blood Glucose↗

Lack of effect of hepatic enzyme induction on metabolic control in patients with type 2 (non-insulin-dependent) diabetes.

A placebo-controlled, double-blind crossover study was carried out in 11 non-insulin-dependent (type 2) diabetic patients to find out the effects of a hepatic enzyme inducer (phenobarbital, 100 mg/day for 2 months) on the metabolic control, plasma C-peptide, insulin, serum, and lipoprotein lipid levels. Phenobarbital induced a significant increase in hepatic antipyrine metabolizing activity, but no significant changes were found in fasting or postload blood glucose, plasma C-peptide, or insulin levels during the study. There was a significant increase in serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, as well as in serum total and very low-density lipoprotein triglycerides, during phenobarbital treatment as compared with placebo.

Adult↗

Plasma insulin and serum lipids and lipoproteins in middle-aged non-insulin-dependent diabetic and non-diabetic subjects.

The relationship between fasting plasma insulin and serum lipid and lipoprotein levels was studied in 1982-1983 in Kuopio, East Finland in 225 patients with non-insulin-dependent diabetes mellitus (119 men and 106 women) and 124 non-diabetic controls (65 men and 59 women). Compared to the non-diabetic controls, diabetic subjects showed significantly lower levels of high density lipoprotein (HDL) cholesterol and high density lipoprotein2 (HDL2) cholesterol and higher levels of total triglycerides and very low density lipoprotein (VLDL) triglycerides. Fasting plasma insulin correlated significantly with total triglycerides and VLDL triglycerides and negatively with HDL cholesterol and HDL2 cholesterol in both male and female diabetic subjects and non-diabetic control subjects. The correlation between fasting plasma insulin and HDL cholesterol remained statistically significant in non-insulin-dependent diabetic subjects and in female non-diabetic control subjects after adjustment for body mass index, alcohol intake, physical activity, smoking, and fasting plasma glucose. The correlation between fasting plasma insulin and total triglycerides remained significant after adjustment for these variables only in females. By multiple stepwise linear regression analysis, fasting plasma insulin had an independent association with HDL cholesterol in female non-diabetic control subjects and in male diabetic subjects and with triglycerides in female non-diabetic control subjects and in female diabetic subjects. The results show that hyperinsulinemia is related to low HDL cholesterol and HDL2 cholesterol and high total triglycerides and VLDL triglycerides in both non-insulin-dependent diabetic subjects and non-diabetic control subjects. This effect of hyperinsulinemia on lipid and lipoprotein patterns may be one explanation why high plasma insulin can promote accelerated atherosclerosis, particularly in patients with non-insulin-dependent diabetes mellitus.

Adult↗

Fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in non-insulin-dependent diabetics and in control subjects.

We have studied fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in 149 non-insulin-dependent diabetics treated either with diet or oral drugs and in 101 non-diabetic control subjects. Diet-treated diabetics showed the highest fasting, postprandial and post-glucagon C-peptide levels in both sexes. In men, diabetics treated with oral drugs showed lower postprandial and glucagon-stimulated C-peptide levels than control subjects, while in women C-peptide levels in this group of diabetics were similar to those in control subjects. The distribution of individual plasma C-peptide levels was wide in non-insulin-dependent diabetics and control subjects and there was considerable overlapping in plasma C-peptide distribution for diabetics and control subjects. Fasting and post-glucagon plasma C-peptide levels in diabetics showed an inverse association to plasma glucose levels and a positive association to degree of obesity, but no association with the known duration of diabetes.

Adult↗

Repeatability of C-peptide response in glucagon stimulation test.

Measurement of the plasma C-peptide level before and after iv administration of 1 mg of glucagon was repeated four times in 10 elderly non-diabetic subjects and in 20 elderly non-insulin-dependent diabetics treated with diet or oral drugs to assess the repeatability of the C-peptide responses. Plasma C-peptide levels before and after glucagon administration and C-peptide glucose ratios in the four measurements did not differ significantly from test to test either in diabetic or non-diabetic subjects. The results of the present study indicate that the repeatability of C-peptide response to glucagon is very good both in non-insulin-dependent diabetics and in non-diabetic subjects.

Aged↗

Macrovascular complications in relation to hyperinsulinaemia in non-insulin-dependent diabetes mellitus.

Despite suggestive evidence from studies on experimental pathology and cell biology of the arterial wall and from clinical and epidemiological studies on non-diabetic subjects indicating that hyperinsulinaemia might be associated with an increased risk of atherosclerotic vascular disease (ASVD) information concerning the role of hyperinsulinaemia as a risk factor of ASVD in diabetic patients still is circumstantial. A few cross-sectional and still fewer prospective studies in patients with non-insulin-dependent diabetes (NIDDM), including two ongoing studies carried out by our own research group, have shown associations between hyperinsulinaemia and the occurrence of ASVD, but these data still are far from consistent and conclusive. Further studies applying combined clinical and epidemiological approach, building upon the results of experimental research concerning possible mechanisms, are needed for better clarification of the role of hyperinsulinaemia as a risk factor of ASVD in NIDDM.

Adult↗