Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 109 records · Page 6Linked to original sources

PubMed1989

Stimulation of prostacyclin synthesis by physical exercise in type I diabetes.

We examined the effect of short- and long-term exercise on prostacyclin (prostaglandin I2 [PGI2]) and thromboxane A2 (TXA2) synthesis in type I (insulin-dependent) diabetic patients and healthy control subjects. PGI2 synthesis was assessed by determining the urinary excretion of 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha and TX synthesis by measuring TXB2 in serum and urine. In the resting state, prostanoid excretion and concentrations were similar in diabetic and control subjects. During 40 min of ergometric cycling exercise, the urinary excretion of 6-keto-PGF1 alpha (a hydration product of vasodilatory PGI2) increased 5.8-fold more in the 12 control subjects than in the 15 diabetic patients (P less than .02). Serum TXB2 concentration rose similarly in diabetic patients and control subjects (P less than .05). During a 75-km competitive cross-country ski race (7 h, 30 min), urinary excretion of 6-keto-PGF1 alpha rose 1.9-fold in 7 diabetic (P less than .05) and 3.3-fold in 10 control (P less than .001) subjects, whereas urinary dinor excretion, reflecting vascular PGI2 synthesis more closely, increased only in the control subjects (P less than .01). Urinary TXB2 excretion remained unchanged in both groups during long-term exercise. These data suggest that diabetic patients have normal PGI2 and TXA2 synthesis in the resting state but diminished PGI2 response to both acute and prolonged exercise.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

The adjustment of diet and insulin dose during long-term endurance exercise in type 1 (insulin-dependent) diabetic men.

We examined in 2 consecutive years the effect of a 75-km (greater than 7 h) cross country skiing on dietary and insulin requirements and glycaemic control in 9 Type 1 (insulin-dependent) diabetic patients. In the first year, the patients were hyperglycaemic (20.9 +/- 1.8 mmol/l) before the race due to excessive carbohydrate loading (65 g) and reduction (by 58%) of short-acting insulin for breakfast. In the second year, breakfast included less carbohydrate (40 g) and more protein, and the morning short-acting insulin was reduced by 35%. With this adjustment of therapy the pre-exercise hyperglycaemia was less (p less than 0.05). The morning intermediate-acting insulin was reduced by 28 and 38% in consecutive years. During both races carbohydrate intake approximated 40 g/h, and blood glucose was maintained at near normal levels after 33 km of skiing. Hypoglycaemia did not occur during exercise, but one patient had symptomatic hypoglycaemia after finishing the second race. The day after exercise insulin sensitivity was increased in all four patients studied. Insulin treated patients can perform strenuous long-term exercise and maintain near normoglycaemia with a proper adjustment of therapy. Augmented insulin sensitivity may contribute to post-exercise hypoglycaemia.

Adult↗

PubMed1988

Glucose and lipid metabolism and insulin sensitivity in type 1 diabetes: the effect of guar gum.

The effect of guar gum on glucose and lipid metabolism and on body insulin sensitivity was examined in nine type 1 diabetic patients treated with continuous subcutaneous insulin infusion. The study was done in a randomized, double-blind, crossover fashion with either guar gum or a placebo added to the usual diet four times per day for 4 wk each. Blood glucose levels after breakfast and lunch and daily insulin requirements were significantly lower during the guar-gum than the placebo diet. After a 4-wk guar-gum supplementation, blood glucose response to a test meal was significantly reduced by guar gum compared with the placebo. Hemoglobin A1 (HbA1) and insulin sensitivity remained unchanged. Serum total cholesterol fell by 21% (p less than 0.025). Thus, guar gum can reduce postprandial blood glucose, insulin requirements, and serum total cholesterol levels in type 1 diabetic patients.

Adult↗

PubMed1988

Acute effects of ethanol and acetate on glucose kinetics in normal subjects.

We compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low (blood ethanol 4 +/- 1 mmol/l) or moderate (14 +/- 1 mmol/l) ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited (0.4-0.5 mg.kg-1.min-1, P less than 0.01) basal glucose production. The decrease in Ra was matched by a comparable decrease in glucose utilization (Rd), resulting in maintenance of normoglycemia. During hyperinsulinemia (approximately 70 microU/ml), glucose disposal was lower (1.2-1.7 mg.kg-1.min-1, P less than 0.01) in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, 1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on Ra is counterbalanced by equal inhibition of Rd;2) basal Ra and Rd are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and 3) acetate is not the mediator of ethanol-induced insulin resistance.

Acetates↗

PubMed1988

Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein.

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.

Adult↗

PubMed1988

The acute effect of ethanol on counterregulatory response and recovery from insulin-induced hypoglycemia.

We examined the acute effect of moderate ethanol administration (oral and iv) on the counterregulatory response and recovery from insulin-induced hypoglycemia after an overnight fast in eight normal men, aged 26 +/- 6 yr. While ethanol increased fasting plasma glucose and serum insulin concentrations, after insulin administration plasma glucose concentrations fell to similar nadirs in the ethanol [2.5 +/- 0.2 (+/- SE) mmol/L] and control studies (2.3 +/- 0.1 mmol/L). The hypoglycemia-induced serum GH, cortisol, and glucagon responses were all reduced (P less than 0.05-0.005) during the ethanol study, while the rises in plasma epinephrine and norepinephrine concentrations were similar in both studies. After discontinuation of the insulin infusions, the initial recovery from hypoglycemia occurred sooner in the presence than in the absence of ethanol. These data indicate that ethanol facilitates the recovery from insulin-induced hypoglycemia in the face of reduced counterregulatory hormones responses. Thus, other mechanisms, such as ethanol-induced insulin resistance, may be important in facilitating the recovery from insulin-induced hypoglycemia during ethanol administration.

Adult↗

PubMed1988

No sign of amyloidosis in pump-treated diabetics.

Serum concentrations of amyloid A (SAA) and C-reactive protein (CRP) were measured in 122 diabetic patients treated by continuous insulin infusion, 40 patients receiving conventional injection therapy and in 28 healthy controls. Of the patients on pump therapy, 63 had an implanted, constant basal rate device (36 i.p., 27 i.v.) and 59 extracorporal, portable programmable pumps (8 i.p., 3 i.v., 48 s.c.). SAA and CRP-values did not significantly differ between the diabetics, irrespective of the method of insulin substitution used, and the healthy controls. Elevated SAA-levels were either associated with raised CRP, indicating a non-specific acute phase reaction, or were markedly diminished or normalized in a six-month follow-up, in spite ongoing pump therapy. Increased SAA-concentrations did not correlate with sex or age of patients, diabetes duration, diabetes type, duration of pump treatment, route of insulin, insulin preparation, catheter material and pump model, indicating that pump treatment does not stimulate a specific amyloidogenic reaction.

Adult↗

PubMed1987

A crossover comparison of continuous insulin infusion and conventional injection treatment of type I diabetes.

We evaluated the feasibility and effectiveness of continuous subcutaneous insulin infusion therapy (CSII) as compared to conventional injection treatment (CIT) in an ordinary diabetic clinic in a one-year randomized crossover study of 65 type I diabetic patients. Home blood glucose levels were lower during CSII (8.6 +/- 0.2 mmol/l, mean +/- SEM) than during CIT (9.1 +/- 0.3 mmol/l, p less than 0.05). During the first six months, HbA1 fell on CSII therapy (from 10.6 +/- 0.4 to 9.7 +/- 0.3%, p less than 0.001), whereas no change occurred during CIT. After the crossover, HbA1 decreased again on CSII (p less than 0.05), but rose in patients shifted from CSII to CIT (p less than 0.05). The fall in glycosylated haemoglobin during CSII correlated with the initial HbA1 level (r = 0.54, p less than 0.001). Ketoacidosis was more common during CSII (16 vs. 2 verified episodes). Hypoglycaemia occurred infrequently, without difference between CSII and CIT. Fifty-six per cent of the patients preferred CSII after the study. In conclusion, while CSII slightly improves the metabolic control, the improvement in the unselected study population is less than previously reported among highly selected patients.

Adolescent↗

PubMed1987

Glucose intolerance and insulin resistance accompany immobilization.

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity, we measured oral glucose tolerance (OGTT) and insulin response to glucose in 18 patients immobilized to bed for six weeks after acute spine fracture. The results were compared to those of nine chronically immobilized spinal cord injury patients and to eight healthy mobile controls. During the first week after trauma both glucose and insulin responses in the OGTT were two- to three-fold above normal (p less than 0.01). The index of insulin resistance (glucose area X insulin area) was seven-fold greater than in healthy controls (p less than 0.001). After three weeks' immobilization insulin resistance had declined by 30-35% (p less than 0.05) being then at the level observed in chronically immobilized subjects. After remobilization the insulin resistance was further decreased but remained still 2.3 times higher than in controls. Thus, trauma causes a manifold increase in insulin resistance, which is reduced but not normalized during the subsequent immobilization and remobilization.

Adolescent↗

PubMed1987

Effect of exercise on insulin binding and glucose transport in adipocytes of normal humans.

Acute exercise increases insulin binding to its receptors on blood cells. Whether the enhanced insulin binding explains the exercise-induced increase in glucose uptake is unclear, since insulin binding and glucose uptake have not been measured simultaneously in a target tissue of insulin. In this study, we determined insulin binding and the rate of glucose transport in adipocytes obtained by needle biopsy from 10 healthy men before and after 3 h of cycle-ergometric exercise. During the exercise, plasma glucose (P less than 0.01) and insulin (P less than 0.001) fell and serum free fatty acid level rose 4.3-fold (P less than 0.001). 125I-insulin binding to adipocytes remained unchanged during exercise. The rate of basal glucose transport clearance fell from 28.1 +/- 5.7 fl.cell-1.s-1 to 22.9 +/- 5.6 fl.cell-1.s-1 (P less than 0.005), and the insulin-stimulated increase in glucose transport rate rose from 196 +/- 26 to 279 +/- 33% (P less than 0.025) during the exercise. Thus, in the adipocytes during exercise, the basal glucose transport rate and the responsiveness of glucose transport to insulin changed in the absence of alterations in insulin binding. These data indicate that the exercise-induced changes in insulin binding show tissue specificity and do not always parallel alterations in glucose transport.

Adipose Tissue↗

PubMed1987

Continuous insulin infusion therapy and retinopathy in patients with type I diabetes.

The effect of continuous subcutaneous insulin infusion (CSII) and conventional injection therapy (CIT) on retinopathy was evaluated in a 1-year crossover study (6 + 6 months) with 54 type I diabetic patients. The glycaemic control improved significantly but did not reach euglycaemic levels during CSII (P less than 0.01-0.001), whereas no change was observed during CIT. At baseline, 50% of the patients had no retinopathy, 20% had only minimal changes, 26% had moderate background retinopathy, and 2 patients had proliferative changes. During CSII, the retinopathy grade impaired in 7 patients, whereas no deterioration occurred during CIT. Improvement of retinopathy grading was observed in 2 patients during CSII and in 5 during CIT, respectively. Individual retinal lesions also progressed more and improved less during CSII (12:3) as compared with CIT (10:9). The net impairment in both retinopathy grading and individual lesions was significant during CSII as compared with CIT (P less than 0.05). There was no difference in the baseline characteristics (severity of retinopathy, age, sex, duration of diabetes, insulin dose, blood pressure, serum creatinine), in the fall of glycosylated haemoglobin or number of hypoglycaemic episodes between the patients with and without worsening of retinopathy during CSII. The present study suggests that even a moderate improvement in metabolic control induced by CSII may be associated with a risk of progression of retinopathy during the first months of therapy.

Adolescent↗

PubMed1987

Hyperglycemia decreases glucose uptake in type I diabetes.

It has recently been postulated that hyperglycemia per se may contribute to insulin resistance in diabetes. To examine this possibility directly, we measured glucose uptake after 24 h of hyperglycemia (281 +/- 16 mg/dl) and normoglycemia (99 +/- 6 mg/dl) in 10 type I (insulin-dependent) diabetic patients (age 33 +/- 3 yr, relative body wt 102 +/- 3%) treated with continuous subcutaneous insulin infusion. Hyperglycemia was induced by an intravenous glucose infusion, whereas saline was administered during the control day. During both studies the patient received a similar diet and insulin dose. After hyper- and normoglycemia, a primed continuous infusion of insulin (40 mU X m-2 X min-1) was started, and plasma glucose was adjusted to and maintained at 142 +/- 2 and 140 +/- 2 mg/dl, respectively, during 60-160 min of insulin infusion. The rate of glucose uptake after hyperglycemia averaged 8.3 +/- 1.1 mg X kg-1 X min-1, which was lower than the rate after the normoglycemic period (10.1 +/- 1.2 mg X kg-1 X min-1, P less than .001). In conclusion, short-term hyperglycemia reduces glucose uptake in type I diabetic patients. Thus, part of the glucose or insulin resistance in these patients may be caused by hyperglycemia per se.

Adult↗

PubMed1986

Natural course of insulin resistance in type I diabetes.

To examine the natural course of insulin action in Type I diabetes, we followed 15 patients prospectively for one year after the diagnosis of diabetes and also performed a cross-sectional study of 53 additional patients who had had diabetes for 2 to 32 years. Two weeks after diagnosis, the rate of glucose uptake during hyperinsulinemia, a measure of insulin action, was 32 percent lower in the patients with diabetes than in 30 matched normal subjects (P less than 0.01), but it rose to normal during the subsequent three months. At three months after diagnosis, 9 of 21 patients (43 percent) were in clinical remission and did not require insulin therapy. In these patients, insulin action was 40 percent greater (P less than 0.002) than in the patients who continued to need insulin treatment. Fasting plasma C-peptide levels were slightly but not significantly higher in the patients who had a remission than in the other patients. In patients who had had diabetes for one year or more, insulin action was also reduced by an average of 40 percent (although there was considerable variation between patients), and it was inversely related to glycemic control and relative body weight. Thus, in patients with newly diagnosed Type I diabetes, a transient normalization of insulin action may occur after an initial reduction, along with a partial recovery of endogenous insulin secretion, and these events may contribute to the development of a clinical remission ("honeymoon" period). A majority of patients with diabetes of long duration are characterized by varying degrees of insulin resistance.

Adult↗

PubMed1986

Physical training and insulin sensitivity.

In conclusion, a large body of available evidence indicates that the degree of physical conditioning is an important determinant of insulin sensitivity and overall glucose tolerance. Both acute exercise and chronic physical training are associated with enhanced disposal of a glucose load. Conversely, physical inactivity leads to a deterioration in glucose tolerance. The primary tissue responsible for accelerated glucose disposal following exercise is muscle. After an acute bout of exercise, enhanced glucose transport and augmented glycogen synthesis are largely responsible for the improvement in glucose tolerance. The beneficial effects of chronic physical training on glucose metabolism appear to be explained by multiple factors, including increased muscle mass, augmented muscle blood flow and capillary area, enhanced mitochondrial oxidative enzyme capacity, and activation of the glucose transport system. Despite these well-documented effects of training on glucose metabolism, the precise role of exercise in the treatment of diabetic patients remains to be established. In insulin-dependent (type I) diabetic individuals, acute exercise has been shown to be a helpful adjunct in establishing good glycemic control. However, the role of acute exercise in helping to smooth out glycemic control in non-insulin-dependent (type II) diabetic patients has received little attention. The role of chronic physical training in the treatment of both insulin-dependent (type I) and non-insulin-dependent (type II) diabetic individuals remains to be established.

Diabetes Mellitus, Type 1↗

PubMed1986

Smoking and insulin sensitivity in type I diabetic patients.

Smoking increases counterregulatory hormone secretion and reduces capillary flow, both of which could reduce insulin mediated glucose disposal. To evaluate whether smoking has any effect on body sensitivity to insulin, we measured insulin-mediated glucose disposal (1 mU euglycemic insulin clamp) during acute smoking in seven male type I diabetic patients. In addition, we performed a cross-sectional study to compare insulin sensitivity in 12 habitually smoking and 22 nonsmoking diabetic patients matched for age, relative body weight, sex, diabetes duration, HbA1, C-peptide, and insulin dose. In the acute study, baseline counterregulatory hormone levels were comparable in the smoking and control experiment. During smoking (9 to 12 cigarettes), carboxyhemoglobin level rose by 57% (P less than 0.01). Circulating adrenaline, cortisol, growth hormone, and glucagon levels were 40% to 100% higher during smoking than during the control clamp study (P less than 0.05-0.01). During acute smoking the rate of insulin-mediated glucose uptake (7.3 +/- 1.0 mg/kg/min) was not significantly different from that without cigarettes (6.8 +/- 0.7 mg/kg/min). In the cross-sectional study, the rate of glucose uptake was comparable in habitually smoking (5.0 +/- 0.5 mg/kg/min) and nonsmoking patients (4.8 +/- 0.3 mg/kg/min). Thus, inspite of a significant rise in counterregulatory hormones, neither acute nor habitual smoking causes substantial changes in insulin sensitivity in type I diabetics.

Adult↗

PubMed1986

The effect of exogenous hyperinsulinemia on proinsulin secretion in normal man, obese subjects, and patients with insulinoma.

To examine possible feedback inhibition of insulin on proinsulin secretion, we measured serum proinsulin levels before and after 120 min of euglycemic hyperinsulinemia (90-100 mU/liter) in 11 normal and 7 obese hyperinsulinemic subjects and 6 patients with beta-cell adenoma (n = 4), carcinoma, or hyperplasia. Baseline proinsulin levels accounted for 19%, 14%, and 56% of the total immunoreactive insulin in the 3 groups, respectively. Compared to normal subjects, baseline proinsulin levels were elevated (P less than 0.02) by 4- and 6-fold in obese subjects and patients with autonomous insulin secretion, respectively, but there was an overlap between the groups. In both normal and obese subjects, hyperinsulinemia suppressed proinsulin secretion by 45-50% (P less than 0.02), whereas no response occurred in the patients. Thus, the 120 min values were clearly different in the patients and the normal or obese subjects. After removal of the adenoma in 4 patients, baseline proinsulin levels and the response to hyperinsulinemia were normalized, but they remained elevated after a partial pancreatectomy or tumor removal in the patients with beta-cell hyperplasia or carcinoma. Thus, proinsulin secretion is under negative feedback control of insulin in both normal man and hyperinsulinemic obese subjects. In patients with insulinoma or beta-cell hyperplasia, this control is lost.

Adenoma, Islet Cell↗

PubMed1986

No association between retinopathy and insulin resistance in type 1 diabetes.

Intact endothelial cell function has been suggested to be important for insulin action. An association between retinopathy and insulin resistance has been found in type 2 diabetes. To evaluate, whether insulin resistance is related to retinopathy in insulin dependent diabetes, we examined 36 type 1 diabetic patients with various degrees of retinopathy: 7 patients had proliferative, 15 had background and 14 patients had no retinopathy. The three groups were matched for age, sex, body weight and insulin dose. Compared with patients with no retinopathy, those with proliferative retinopathy had a longer (P less than 0.05) duration of diabetes (13 +/- 3 vs 22 +/- 3 years for no vs proliferative retinopathy), and higher (P less than 0.05) serum creatinine (74 +/- 4 vs 97 +/- 8 mumol/l), triglyceride (0.69 +/- 0.04 vs 1.02 +/- 0.17 mmol/l) and diastolic blood pressure (77 +/- 3 vs 90 +/- 10 mmHg) levels. The rate of insulin-mediated glucose metabolism (1 mU euglycaemic insulin clamp) was virtually identical in each diabetic group (4.80 +/- 0.42, 4.90 +/- 0.36 and 4.98 +/- 0.74 mg/kg/min) and 40% below that in 8 matched normal subjects (7.53 +/- 0.53 mg/kg/min, P less than 0.001). In conclusion, proliferative retinopathy is related to long duration of diabetes, incipient nephropathy and hypertension. Insulin resistance characterizes the majority of patients with type 1 diabetes but is unrelated to retinopathy.

Adult↗

PubMed1986

Relationship between oral glucose tolerance and insulin sensitivity in healthy man and type 1 diabetic patients.

The relationship between insulin sensitivity and oral glucose tolerance was studied in 8 conventionally treated type 1 diabetic patients (age 34 +/- 4 years, relative body weight (RBW) 113 +/- 5%) and in 11 healthy subjects (age 35 +/- 3 years, RBW 114 +/- 2%). In each subject and patient, oral glucose tolerance (75 g glucose) and in vivo sensitivity to insulin (euglycaemic clamp technique, 1 mU/kg/min insulin) were measured. The response to oral glucose in the diabetic patients was measured during maintenance of similar peripheral plasma free insulin levels as in the normal subjects during the oral glucose tolerance test (OGTT). During the OGTT, the post-glucose plasma glucose values in the diabetic patients were markedly higher (P less than 0.001) than in the normal subjects. During the clamp study, the rate of glucose metabolism in the diabetic patients (4.53 +/- 0.58 mg/kg/min) was 37% lower than in the normal subjects (7.19 +/- 0.67 mg/kg/min, P less than 0.02). The area under the glucose curve was inversely related to the rate of glucose metabolism in both the diabetic (r = -0.72, P less than 0.02) and the normal (r = -0.69, P less than 0.02) subjects. The slope of the curve was substantially steeper in the diabetic than the control subjects. Thus, peripheral insulin sensitivity contributes to oral glucose tolerance both in healthy man, and even to a greater extent, in type 1 diabetic patients.

Adult↗