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Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 127 records · Page 7Linked to original sources
PubMed1986

Pathogenesis and prevention of the dawn phenomenon in diabetic patients treated with CSII.

The mechanism of the dawn phenomenon was studied in 12 C-peptide-negative type I diabetic patients (age 30 +/- 2 yr) treated with continuous subcutaneous insulin infusion. During constant basal infusion, nocturnal glycemia remained constant until 4 a.m., but began to rise thereafter in 10/12 patients, with the mean rise from 4.6 +/- 0.4 mmol/L to 6.1 +/- 0.7 mmol/L (P less than 0.01) by 8 a.m. In these patients the rate of glucose production (Ra, 2.14 +/- 0.04 mg/kg/min, 3-H3-glucose infusion) exceeded the rate of utilization (Rd, 1.89 +/- 0.03 mg/kg/min, P less than 0.02). When the patients were restudied after the infusion rate was increased by 49 +/- 7%, Ra fell to 1.75 +/- 0.03 mg/kg/min (P less than 0.01) and the dawn phenomenon was abolished. However, both Ra and Rd remained higher in the diabetic subjects (P less than 0.05) than in eight healthy control subjects, in whom Ra (1.66 +/- 0.02 mg/kg/min) was equal to Rd with glycemia remaining unchanged. Peripheral free insulin levels in the diabetic patients were similar during constant (12.3 +/- 0.5 mU/L) and increased infusion rate (11.3 +/- 0.4 mU/L), and higher than those of the control subjects (5.2 +/- 0.2 mU/L, P less than 0.05). A diurnal rise in serum cortisol levels occurred 1 h earlier in the diabetic than in the control subjects, and Ra was directly proportional to serum cortisol concentration (r = 0.61, P less than 0.01). Serum growth hormone levels were also slightly higher in the diabetic than the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Failure to suppress C-peptide secretion by euglycaemic hyperinsulinaemia: a new diagnostic test for insulinoma?

In order to study the suppression of C-peptide secretion in 5 patients with insulin-producing tumours or beta cell hyperplasia, we raised and maintained plasma insulin at a high physiological level and kept plasma glucose unchanged for 2 h with combined infusions of glucose and insulin (insulin clamp technique). No suppression of C-peptide secretion was seen in any of the patients, in contrast with a 35-65% decline seen in each of 17 healthy control subjects. In 3 patients surgical removal of beta cell adenoma normalized the response, whereas it remained unchanged in a patient with beta cell hyperplasia after partial pancreatectomy and in another with inoperable carcinoma. These results indicate that insulin secretion by insulinomas is characterized by lack of suppression by insulin. Measurement of the insulin-insulin feedback loop by the clamp technique may provide a rapid test to reveal autonomous insulin secretion without the risk of hypoglycaemia.

Adenoma, Islet Cell↗
PubMed1985

Influence of body composition on insulin clearance.

The effect of body composition on clearance of infused insulin was studied in 21 young normal weight (relative body weight 107 +/- 2%, of ideal mean +/- SEM) healthy subjects. In each subject, the per cent of body weight made up of muscle and fat tissue (% muscle and % fat) were determined. Clearance of insulin was estimated during infusion of insulin at the rate of 40 mU/m2/min under maintenance of normoglycaemia using the euglycaemic clamp technique. Steady-state plasma insulin levels (92.6 +/- 3.2 mU/litre) correlated negatively with % muscle (r = -0.60, P less than 0.01), and positively with % fat (r = 0.55, P less than 0.01). Clearance of insulin was directly related to % muscle (r = 0.60, P less than 0.01), and inversely related to % fat (r = -0.48, P less than 0.01). Steady-state plasma insulin levels or insulin clearance did not correlate with relative body weight. Multiple linear regression analysis revealed a significant multivariate correlation between the rate of insulin clearance versus % muscle and % fat (r = 0.62, P less than 0.02). The changes in % muscle and % fat could predict 37% of the observed interindividual variance of insulin clearance. These results indicate that insulin clearance depends on body composition and is higher in muscular than in adipose subjects. This difference may reflect either a greater distribution space of insulin in muscular as compared to adipose subjects or an influence of body composition on insulin catabolism.

Adipose Tissue↗
PubMed1985

Glycogen depletion during prolonged exercise: influence of glucose, fructose, or placebo.

We examined the influence of various carbohydrates of fuel homeostasis and glycogen utilization during prolonged exercise. Seventy-five grams of glucose, fructose, or placebo were given orally to eight healthy males 45 min before ergometer exercise performed for 2 h at 55% of maximal aerobic power (VO2max). After glucose ingestion, the rises in plasma glucose (P less than 0.01) and insulin (P less than 0.001) were 2.4- and 5.8-fold greater than when fructose was consumed. After 30 min of exercise following glucose ingestion, the plasma glucose concentration had declined to a nadir of 3.9 +/- 0.3 mmol/l, and plasma insulin had returned to basal levels. The fall in plasma glucose was closely related to the preexercise glucose (r = 0.98, P less than 0.001) and insulin (r = 0.66, P less than 0.05) levels. The rate of endogenous glucose production and utilization rose similarly by 2.8-fold during exercise in fructose group and were 10-15% higher than in placebo group (P less than 0.05). Serum free fatty acid levels were 1.5- to 2-fold higher (P less than 0.01) after placebo than carbohydrate ingestion. Muscle glycogen concentration in the quadriceps femoris fell in all three groups by 60-65% (P less than 0.001) during exercise. These data indicate that fructose ingestion, though causing smaller perturbations in plasma glucose, insulin, and gastrointestinal polypeptide (GIP) levels than glucose ingestion, was no more effective than glucose or placebo in sparing glycogen during a long-term exercise.

Adult↗
PubMed1984

Remissions in newly diagnosed type 1 (insulin-dependent) diabetes: influence of interferon as an adjunct to insulin therapy.

We studied the effect of interferon as an adjunct to conventional insulin therapy on the early course of Type 1 diabetes in 43 newly diagnosed patients. Compared with conventional therapy, interferon administration slightly delayed the improvement of glucose homeostasis and the rise of high density lipoprotein cholesterol, while C-peptide secretion was unaffected. Independent of the type of therapy, 18 patients (42%) entered partial remission. The remission began 2.0 +/- 0.6 months (mean +/- SEM) from the start of therapy and lasted for 4.1 +/- 1.1 months. Seven patients (16%) were still in remission 1 year after diagnosis. The patients who entered remission had higher initial C-peptide secretion, lower glycosylated haemoglobin levels and better initial control than patients without remission. Thus, interferon provided no benefits as an adjunct to conventional insulin therapy in unselected patients with newly diagnosed Type 1 diabetes. An important factor for the development of remission was the presence of C-peptide secretion at the time of diagnosis.

Adolescent↗
PubMed1984

Response of adipose tissue lipoprotein lipase activity and serum lipoproteins to acute hyperinsulinaemia in man.

In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p less than 0.01) and during hyperglycaemic clamp (p less than 0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r = -0.67), during hyperglycaemic clamp (r = -0.68) and during infusion of saline (r = -0.75, p less than 0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p less than 0.05) during the high-insulin clamp and by 10% (p less than 0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

Glucose tolerance, plasma lipoproteins and tissue lipoprotein lipase activities in body builders.

Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118 +/- 4%), eight weight-matched (RBW 120 +/- 5%) and seven normal-weight controls (RBW 111 +/- 3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P less than 0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P less than 0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and VO2max. Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL2 and HDL3 cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Continuous subcutaneous insulin infusion therapy decreases insulin resistance in type 1 diabetes.

The influence of continuous sc insulin infusion therapy for 6 weeks on sensitivity to insulin (euglycemic clamp technique) and hepatic glucose production (3-[3H]glucose technique) was measured in 10 type 1 diabetic patients whose mean duration of diabetes was 8 yr. Mean diurnal blood glucose fell from 8.5 +/- 0.8 (SEM) mmol/liter to 6.0 +/- 0.6 mmol/liter (P less than 0.05) and glycosylated hemoglobin from 10.5 +/- 0.4% to 8.7 +/- 0.3%. Insulin requirements declined by 23% from 47 +/- 4 U/day prepump to 36 +/- 2 U/day after 6 weeks of pump therapy (P less than 0.01). During the insulin clamp, plasma insulin was maintained at approximately 90 mU/liter and plasma glucose at approximately 5.0 mmol/liter in all studies. The rate of glucose metabolism in diabetic patients during conventional therapy (4.65 +/- 0.41 mg/kg X min) was 35% lower than in normal subjects (7.20 +/- 0.42 mg/kg X min, n = 14, P less than 0.001). After 6 weeks of pump therapy, total glucose uptake increased by 27% to 5.90 +/- 0.60 mg/kg X min, P less than 0.05 vs. prepump). This was still 18% lower than in the normal subjects (P less than 0.05). Basal hepatic glucose production in the diabetic patients during conventional therapy (3.07 +/- 0.14 mg/kg X min) was 70% higher than in the normal subjects (1.79 +/- 0.07 mg/kg X min, n = 7, P less than 0.001). After 6 weeks of pump therapy, hepatic glucose production fell to 2.48 +/- 0.19 mg/kg X min (P less than 0.05), which was still 40% higher than in the normal subjects (P less than 0.01). Basal hepatic glucose production was directly related to the fasting plasma glucose level (r = 0.67, P less than 0.001) and inversely proportional to fasting insulin concentration (r = -0.48, P less than 0.05) in the diabetic patients. Specific tracer insulin binding to erythrocytes in the diabetic patients (19.4 +/- 1.5%) was comparable to that in the normal subjects (19.6 +/- 1.2%) and remained unchanged during pump therapy. Thus the improved metabolic control resulting from pump therapy is associated with enhancement in sensitivity to insulin, and reduction in basal hepatic glucose production.

Adult↗
PubMed1984

Insulin sensitivity in newly diagnosed type 1 diabetics after ketoacidosis and after three months of insulin therapy.

Tissue sensitivity to insulin (euglycemic insulin clamp technique), hepatic glucose production (3-[3H]glucose infusion) and insulin binding to erythrocyte receptors were studied in 14 newly diagnosed type 1 diabetic patients after the disappearance of ketosis and after 3 months of insulin therapy. The control group consisted of 14 normal subjects. During the two insulin clamp studies, plasma glucose in the diabetic patients was maintained at 5.0 +/- 0.04 (SEM) mmol/liter and 4.9 +/- 0.05 mmol/liter, with corresponding steady state free insulin levels of 90 +/- 4 mU/liter, and 67 +/- 6 mU/liter (P less than 0.02) during the first and second study, respectively. The decline in free insulin levels was due to the development of insulin antibodies during insulin therapy (10 +/- 0.1% vs. 18 +/- 2%, P less than 0.001, serum insulin-binding capacity during the first and second study, respectively). In the normal subjects, steady state plasma glucose and insulin levels were 4.9 +/- 0.1 mmol/liter and 89 +/- 4 mU/liter, respectively. The rate of glucose metabolism (M) in the diabetic patients during the first study (5.13 +/- 0.65 mg/kg X min) was 35% lower than that in the normal subjects (7.94 +/- 0.50 mg/kg X min, P less than 0.005). After 3 months of insulin therapy, M increased by 35% to 6.92 +/- 0.58 mg/kg X min, which was comparable to that in the normal subjects. To compensate for the difference in plasma free insulin levels, we calculated an index for insulin sensitivity by dividing M by the ambient insulin concentration (I). During the 3 months of insulin therapy, M/I rose 2-fold to 11.63 +/- 1.10 mg/kg X min per mU insulin/liter X 100, which was similar to that in normal subjects (9.16 +/- 0.67 mg/kg X min per mU insulin/liter X 100). Five diabetic patients had a partial clinical remission, as determined by normal fasting C-peptide levels. In these patients, insulin sensitivity was 35-50% greater than in those who failed to have a remission (P less than 0.05). Basal hepatic glucose production in the diabetic patients during the first study (2.78 +/- 0.14 mg/kg X min) was 56% higher than in the normal subjects (1.78 +/- 0.04 mg/kg X min, P less than 0.001), and remained unchanged during insulin therapy. During the hyperinsulinemia induced by the clamp, hepatic glucose production was totally suppressed in both the diabetic and control subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

Site of insulin resistance in type 1 diabetes: insulin-mediated glucose disposal in vivo in relation to insulin binding and action in adipocytes in vitro.

To evaluate the mechanism of insulin resistance in type 1 diabetes mellitus, we measured insulin sensitivity in vivo and insulin action in adipocytes in vitro. The study groups consisted of 18 insulin-treated type 1 diabetic patients and 14 matched normal subjects. In each subject, insulin-mediated glucose disposal in vivo was measured by the euglycemic clamp technique. An open surgical biopsy was performed in 9 diabetic and 7 healthy subjects to obtain abdominal sc adipose tissue for the measurement of [125I]insulin binding, D-[14C]-glucose transport, oxidation, and lipogenesis. During the euglycemic clamp studies, similar steady state plasma glucose (4.8 mmol/liter) and insulin (80 mU/liter = 700 pM) levels were maintained in both groups. The rate of glucose metabolism (M) was 43% lower in the diabetic patients (4.75 +/- 0.34 mg/kg X min) than in the normal subjects (8.27 +/- 0.43 mg/kg X min; P less than 0.001). [125I]Insulin binding to adipocytes was reduced in the diabetic patients (26% reduction in tracer binding; P less than 0.05) due to a reduction in receptor number. Insulin binding was not related to the M value at any insulin concentration. Basal and insulin-stimulated rates of glucose transport were not significantly different in diabetic and normal subjects. The basal glucose oxidation rate was reduced by 50% (P less than 0.02), and maximal glucose oxidation was reduced by 49% (P less than 0.03) in the diabetic patients (237 +/- 30 vs. 359 +/- 49 pmol/30,000 cells X 90 min, basal vs. maximal glucose oxidation, respectively) compared to those in normal subjects (513 +/- 101 vs. 700 +/- 133 pmol/30,000 cells X 90 min). The percentage responses of glucose oxidation and glucose transport to insulin were similar in both groups. Glucose oxidation rates at basal (r = 0.68; P less than 0.01), half-maximally (ED50; r = 0.70; P less than 0.01), and maximally (r = 0.64; P less than 0.05) effective insulin concentrations were positively related to the M value. Basal and insulin-stimulated rates of lipogenesis were comparable between the diabetic and normal subjects. In conclusion, insulin-mediated glucose disposal in vivo is reduced in conventionally treated type 1 diabetic patients. In vitro, adipocytes from diabetes bound slightly less insulin at tracer insulin concentrations, but the magnitude of this reduction was not related to impairment of glucose metabolism in vivo. Of the pathways of glucose metabolism studied, the rate of glucose oxidation was most affected. A significant relationship was found between the M value and the rate of in vitro glucose oxidation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1984

Human and porcine insulins are equally effective in the regulation of glucose kinetics of diabetic patients during exercise.

The rate of hepatic glucose production (Ra) and peripheral utilization (Rd) was determined in 8 insulin-dependent diabetic subjects in basal state and during 40 min cycle ergometric exercise. The patients were treated with continuous sc infusion of either semisynthetic human or porcine (Actrapid) insulin. Basal rate of glucose production was comparable during human (2.29 +/- 0.19 mg/kg/min) and porcine (2.18 +/- 0.12 mg/kg/min) insulin therapy. In response to exercise, Ra rose 30 to 40% (P less than 0.05), to 2.85 +/- 0.35 vs 3.18 +/- 0.42 mg/kg/min, similarly during both studies. The peak rise in Rd (to 3.20 +/- 0.32 during human vs 3.78 +/- 0.44 mg/kg/min during porcine insulin) was comparable in both groups and not significantly different from the rise in Ra. Consequently, blood glucose levels remained unchanged. During the exercise tests, the metabolic conditions were stable and comparable in both studies, as indicated by similar levels of blood glucose, plasma free insulin HbA1, serum lipids and insulin binding to erythrocytes. In conclusion, semisynthetic human insulin is equally effective as porcine insulin in regulating glucose kinetics in the basal state and during exercise.

Adult↗
PubMed1983

No evidence of amyloidosis in type I diabetics treated with continuous subcutaneous insulin infusion.

A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated with continuous subcutaneous insulin infusion and in five conventionally treated patients. Only one pump- and one conventionally treated patient had detectable but low SAA levels, comparable with these seen in healthy controls. In patients with secondary amyloidosis the mean SAA level was 24-fold higher than in controls (P less than 0.001). Similarly, in both diabetic groups, AFDA was normal whereas it was reduced by 41% in patients with amyloidosis (P less than 0.001). Furthermore, no local amyloidosis was seen at the infusion site in any of the patients studied. Thus, our data fail to provide any evidence of secondary amyloidosis in patients treated for 3-40 mo with continuous subcutaneous insulin infusion.

Adult↗
PubMed1983

Effects of body composition on insulin sensitivity.

We studied the effects of body composition and maximal aerobic power on insulin sensitivity in 23 normal-weight, healthy male subjects. Eight were weight lifters, eight were long-distance runners, and seven were untrained controls. In each subject, the percentage of body weight (BW) made up of muscle and fat tissue (% muscle and % fat, respectively), the maximal aerobic power (VO2max), and the tissue sensitivity to insulin were measured. The weight lifters were characterized by 35% higher % muscle as compared with the runners or controls (P less than 0.01). VO2max in the runners was 30-40% higher than in the weight lifters or controls (P less than 0.001). During the euglycemic clamp studies, similar steady-state plasma glucose and insulin levels were achieved in each group. When calculated per total BW, the rate of glucose metabolism (M) was virtually identical in the weight lifters (10.26 +/- 1.02 mg/kg BW/min) and the runners (10.03 +/- 0.86 mg/kg BW/min), and 4045% higher than in the controls (7.10 +/- 0.75 mg/kg BW/min, P less than 0.05). When calculated per muscle mass (Mm), only the runners had a higher than normal rate of glucose metabolism (P less than 0.02). M was directly proportional to% muscle (r = 0.54, P less than 0.01) and inversely related to % fat (r = -0.72, P less than 0.001). The multiple linear regression analysis revealed a highly significant multivariate correlation between M and the combined effect of % muscle, %fat, and VO2max (r = 0.78, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗