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Biomedical subjects

V A Koivisto

Publications and source records attributed to V A Koivisto.

At least 37 records · Page 2Linked to original sources
PubMed1998

Serum leptin and longevity.

There are changes in the ability to regulate energy balance and caloric intake with aging. Consequently, we investigated whether human aging modifies the levels of serum leptin, a novel hormone implicated in the regulation of energy balance. We studied 268 Caucasian men and women aged 22-85 years, and divided them into groups with mean ages of 30, 40, 50, 65, 75, 80 and 85 years. Fasting serum leptin concentrations were determined by radioimmunoassay. Subjects aged 65 or older were followed for five years after the blood sampling. There were no statistically significant differences in fasting serum leptin concentrations across different age groups in females (p = 0.090). Fasting serum leptin concentrations were also similar in different age groups in males, except that males in the 30-year age group had lower serum leptin levels than males in the 75-year age group (p = 0.042). Leptin levels were 2-3 fold higher in females than in males in each age group (p < 0.005 except p = 0.063 in the 75-year age group). Elderly women, who lived longer, had 47% higher (p < 0.05) serum leptin concentrations, and 17% higher (p < 0.001) BMI than the women who died within five years of blood sampling. Leptin levels were not statistically different in these women after adjusting for BMI. Thus, aging has no apparent effect on serum leptin levels in women or men, and the gender differences in leptin is present also in the older age groups. Higher leptin concentrations in the females who live longer may reflect a better nutritional status, and a greater adipose tissue mass rather than a primary factor for survival.

Aged↗
PubMed1998

Intramuscular triglyceride content is increased in IDDM.

UNLABELLED: Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men (age 29 +/- 2 years, BMI 23.3 +/- 0.6 kg/m2) and 17 men with insulin-dependent diabetes mellitus (IDDM) (age 30 +/- 2 years, BMI 22.8 +/- 0.5 kg/m2, diabetes duration 14 +/- 2 years, HbA1c 7.7 +/- 0.3%, insulin dose 48 +/- 3 U/day). Insulin sensitivity was measured with a 4h euglycaemic (5 mmol/l) hyperinsulinaemic (1.5 mU or 9 pmol x kg(-1) x min[-1]) clamp accompanied by indirect calorimetry before and at the end of the insulin infusion. A percutaneous biopsy was performed from m. vastus lateralis for the determination of mTG. At baseline the IDDM patients had higher glucose (10.2 +/- 0.9 vs 5.6 +/- 0.1 mmol/l, p < 0.001), insulin (40.3 +/- 3.2 vs 23.2 +/- 4.2 pmol/l, p < 0.01), HDL cholesterol (1.28 +/- 0.06 vs 1.04 +/- 0.03 mmol/l, p < 0.01) and mTG (32.9 +/- 4.6 vs 13.6 +/- 2.7 mmol/kg dry weight, p < 0.01) concentrations than the healthy men, respectively. The IDDM patients had lower insulin stimulated whole body total (-25%, p < 0.001), oxidative (-18%, p < 0.01) and non-oxidative glucose disposal rates (-43%, p < 0.001), whereas lipid oxidation rate was higher in the basal state (+ 44%, p < 0.01) and during hyperinsulinaemia (+283%, p < 0.05). mTG concentrations did not change significantly during the clamp or correlate with insulin stimulated glucose disposal. In healthy men mTG correlated positively with lipid oxidation rate at the end of hyperinsulinaemia (r = 0.75, p < 0.05). IN CONCLUSION: 1) IDDM is associated with increased intramuscular TG content. 2) mTG content does not correlate with insulin sensitivity in healthy subjects or patients with IDDM.

Adult↗
PubMed1998

Is brain uptake of leptin in vivo saturable and reduced by fasting?

Leptin is a peptide hormone produced by adipocytes which provides a negative feedback signal to control the amount of body fat. The action of leptin on food intake and weight loss is thought to be mediated by interaction with its hypothalamic receptor. We examined the biodistribution and brain uptake of radioiodinated leptin (123I-leptin) by dynamic gamma imaging in six anaesthetized New Zealand white rabbits. Leptin uptake was seen in the brain, lungs, liver and kidneys. In the brain, increase in radioactivity as a function of time was seen in the choroid plexus area. The choroid plexus to brain radioactivity ratio (CP/BR) was used as the target to background ratio. The CP/BR ratio increased up to approximately 40-60 min, after which a steady state in CP/BR was achieved. The steady state uptake ratio was higher in the rabbits that had fasted for only 6-8 h before the experiment (CP/BR approximately 2.5) than in those that had fasted for 25-27 h before the experiment (CP/BR approximately 1.8). Thus, leptin uptake in vivo occurs in the choroid plexus region of the brain and in the lungs, kidney and the liver. The uptake of leptin in the choroid plexus appears to be saturable, as indicated by the achieved steady state in the CP/BR radioactivity curve 40-60 min following 123I-leptin injection. The lower steady state CP/BR after prolonged fasting may be the result of the downregulation of leptin receptors in the choroid plexus.

Animals↗
PubMed1998

Circulating leptin has saturable transport into intrathecal space in humans.

BACKGROUND: Leptin is an adipocyte-derived hormone that is thought to provide a negative feedback signal to control body fat mass by interacting with its hypothalamic receptor. The present study was undertaken to examine the uptake of leptin in cerebrospinal fluid (CSF) space in humans and whether the transport of leptin into CSF space is an active phenomenon or due to free access through the blood-CSF barrier. METHODS: We determined serum and CSF leptin concentrations by radioimmunoassay in 17 men [42 +/- 4 years, mean +/- SE; body mass index (BMI) 27.3 +/- 1.8 kg m-2] and 22 women (40 +/- 3 years, BMI 25.1 +/- 1.0 kg m-2). The function of the blood-CSF barrier was evaluated by determining the CSF/serum albumin ratio. RESULTS: Serum leptin concentration was lower in male (5.8 +/- 1.6 microgram L-1) than in female subjects (13.1 +/- 1.7 microgram L-1, P = 0. 001), whereas the concentrations of leptin in CSF were virtually identical in male (0.34 +/- 0.03 microgram L-1) and female (0.36 +/- 0. 03 microgram L-1) subjects. Serum leptin was correlated positively with BMI both in men (r = 0.89, P < 0.01, n = 10) and in women (r = 0.61, P < 0.05, n = 14), whereas no correlation between CSF leptin concentration and BMI was found in either group. The CSF/serum leptin ratio correlated negatively with serum leptin concentration both in men (r = -0.93, P < 0.001) and in women (r = -0.77, P < 0. 001) and with BMI both in men (r = -0.75, P = 0.02, n = 10) and in women (r = -0.64, P < 0.02, n = 14). The CSF/serum albumin ratio was not correlated with the CSF/serum leptin ratio in either group. CSF leptin concentrations and the CSF/serum leptin ratio were virtually identical in subjects with impaired and normal blood-CSF barrier function. CONCLUSION: Thus, our data support the presence of a saturable and active transporter of leptin from circulation into intrathecal space.

Adipose Tissue↗
PubMed1998

The effect of exercise on leptin concentration in healthy men and in type 1 diabetic patients.

PURPOSE: Leptin is a recently discovered hormone that appears as a regulator of energy balance. It is important to know whether leptin concentrations are changed under conditions of altered energy homeostasis. Consequently, we examined the effects of exercise with fasting and exercise with feeding on circulating leptin concentrations in healthy men and in type 1 diabetic patients with normal body weight and well controlled diabetes. METHODS: Leptin concentrations were determined with radioimmunoassay. RESULTS: During a 3-h cycle ergometer exercise with fasting, leptin decreased by 42% (P < 0.01) in nine healthy men and by 23% (P = 0.05) in eight male type 1 diabetic patients. Leptin fell equally by 12% (P < 0.03) both in nine healthy men and in eight male type 1 diabetic patients who were studied as a resting control group. The absolute fall in leptin in healthy men was similar in the exercise and resting control groups (0.8 +/- 0.1 microgram.L-1 vs 0.8 +/- 0.2 microgram.L-1). However, due to lower leptin concentration before the exercise, the relative decrease (42%) was greater than during the resting control study (12%, P < 0.005). This difference was not seen in the diabetic patients. Fasting leptin concentration correlated positively with BMI (r = 0.75, P < 0.001) and fasting insulin (r = 0.71, P < 0.01) in healthy men as well as with insulin level (r = 0.54, p < 0.05) in type 1 diabetic patients. When exercise was performed with feeding, and this was associated with a significant rise in serum cortisol level (marathon run, 14 healthy men and 7 type 1 diabetic patients), leptin concentration did not change significantly. CONCLUSIONS: 1) During morning hours, leptin decreases both in healthy men and in type 1 diabetic patients, reflecting a diurnal variation of leptin concentration and the effect of fasting on leptin concentration. 2) The fall in leptin during morning hours is augmented by physical exercise in healthy men. 3) If exercise is performed with feeding and associated with a rise in serum cortisol level, leptin concentration remains unchanged. These data suggest that although exercise may reduce circulating leptin levels, the effect is small and can be counterbalanced by feeding or a rise in serum cortisol concentration.

Adult↗
PubMed1998

Meta-analysis of the effect of insulin lispro on severe hypoglycemia in patients with type 1 diabetes.

OBJECTIVE: A precise time-action profile of insulin lispro (Humalog) at mealtime may reduce the incidence of severe hypoglycemia. Because it is a rare complication, we performed a cumulative meta-analysis to compare the frequency of severe hypoglycemia during insulin lispro and human regular insulin therapy in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: The analysis included eight large multi-center clinical trials, three with parallel and five with crossover designs. The studies included 2,576 type 1 diabetic patients in total, with 2,327 receiving insulin lispro and 2,339 receiving regular human insulin, representing > 1,400 patient-years of insulin therapy Severe hypoglycemia was defined as coma or requiring glucagon or intravenous glucose. The patients received either NPH or ultralente as their basal insulin and insulin lispro or regular human insulin before each meal. RESULTS: Seventy-two patients (3.1%) had a total of 102 severe hypoglycemic episodes during insulin lispro therapy compared with 102 patients (4.4%) with a total of 131 episodes during regular human insulin therapy (P=0.024). CONCLUSIONS: The results of this meta-analysis demonstrate that in type 1 diabetic patients, the frequency of severe hypoglycemia can be reduced by taking insulin lispro as compared with regular human insulin therapy.

Clinical Trials as Topic↗
PubMed1998

Long-term lisinopril therapy reduces exercise-induced albuminuria in normoalbuminuric normotensive IDDM patients.

OBJECTIVE: To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate. RESEARCH DESIGN AND METHODS: A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 +/- 3 years, BMI 24.5 +/- 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 +/- 2 years, BMI 24.4 +/- 0.9 kg/m2). Overnight and exercise-induced urinary albumin excretion rate was measured at baseline and after 1 and 2 years of treatment. Two patients in the placebo group and none in the lisinopril group developed microalbuminuria. RESULTS: In the lisinopril group, the exercise-induced urinary albumin excretion rate diminished 46% after the 1st year (P = 0.059) and 66% (P < 0.01) after the 2nd year. However, it remained unchanged in the control group. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were similar at baseline and after 1 year, but at 2 years, sBP was 13 mmHg lower (P = 0.03) and dBP was 9 mmHg lower (P = 0.052) in the lisinopril group as compared with the control group. The dBP decreased significantly at 1 and 2 years in the lisinopril group, while there was no significant change in the sBP. In the whole group at baseline, the overnight albumin excretion rate correlated with HbA1c (r = 0.50, P < 0.01) and the duration of diabetes (r = 0.39, P < 0.05), and sBP correlated with both the overnight (r = 0.42, P < 0.05) and the exercise-induced (r = 0.48, P < 0.05) albumin excretion rate. CONCLUSIONS: Glycemic control and blood pressure are directly related to the overnight albumin excretion rate also in normotensive normoalbuminuric IDDM patients. Lisinopril treatment reduces the exercise-induced urinary albumin excretion rate in such patients. These data suggest a protective effect of lisinopril against the development of microalbuminuria.

Adult↗
PubMed1998

The human insulin analogue insulin lispro.

Insulin lispro is a newly developed analogue of human insulin where the positions of the amino acids lysine and proline have been switched at the end of the B chain of the insulin molecule. Insulin lispro with lysine at position B28 and proline at position B29 has a weaker tendency for self-association than human insulin. This leads to three major differences in the pharmacokinetics: the action begins faster, has a higher peak and the duration is shorter than with human insulin. Thus, insulin lispro has a more precise action profile for the mealtime than human regular insulin. Insulin lispro is recommended to be injected within 15 min before the meal in contrast to 30-40 min for human insulin. In clinical trials with insulin lispro, the postprandial rise of blood glucose is smaller, the rate of hypoglycaemia is lower particularly at night-time, the need for snacks is smaller and the patient preference is better than with human insulin. The long-term control as reflected by an improvement in the HbA1c level is better with insulin lispro than with human regular insulin, provided that an appropriate basal insulin regimen is used to take into account the shorter duration of action. A few patients have been described who have a severe resistance to human insulin but who have been successfully treated with insulin lispro. Insulin lispro was designed to be used as a mealtime insulin, and it is a step forward in the treatment of diabetic patients using a basal-bolus insulin regimen.

Blood Glucose↗
PubMed1997

Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.

BACKGROUND: Insulin lispro is an insulin analog that was recently developed particularly for a mealtime therapy. It has a fast absorption rate and short duration of action. The efficacy of insulin lispro in the clinical therapy of patients with non-insulin-dependent diabetes mellitus (NIDDM) has not been tested. OBJECTIVES: To compare insulin lispro and human regular insulin in the mealtime treatment of patients with NIDDM. METHODS: A 6-month, randomized, multinational (16 countries), multicenter (80 sites) clinical trial with an open-label, crossover design was performed in 722 patients with NIDDM. Insulin lispro was injected immediately before and human regular insulin 30 to 45 minutes before the meal. RESULTS: Throughout the study, the postprandial rise in serum glucose levels was significantly lower during insulin lispro than human regular insulin treatment. At end point the rise (mean +/- SEM) in serum glucose levels was 30% lower at 1 hour (2.6 +/- 0.1 mmol/L [46.8 +/- 1.8 mg/ dL] for lispro vs 3.7 +/- 0.1 mmol/L [66.6 +/- 1.8 mg/dL] for human regular insulin) and 53% lower 2 hours after the test meal (1.4 +/- 0.1 mmol/L [25.2 +/- 1.8 mg/dL] for lispro vs 3.0 +/- 0.1 mmol/L [54.0 +/- 1.8 mg/dL] for human regular insulin) with insulin lispro compared with human regular insulin therapy (P < .001 for both intervals). During insulin lispro therapy the rate of hypoglycemia overall (P = .01) and overnight (P < .001) was lower and the number of asymptomatic hypoglycemic episodes was smaller (P = .03) than during human regular insulin therapy. Associated with a similar 13% increase (P < .001) in the total daily insulin dose, the glycosylated hemoglobin level decreased (P < .001) equally in both treatment groups. Serum lipid and lipoprotein levels remained unchanged. There were no differences in the adverse events between the 2 treatment groups. CONCLUSIONS: Compared with human regular insulin therapy, mealtime therapy with insulin lispro reduced postprandial hyperglycemia and may decrease the rate of mild hypoglycemic episodes in patients with NIDDM.

Blood Glucose↗
PubMed1997

Relation between plasma leptin levels and measures of body fat in identical twins discordant for obesity.

BACKGROUND: Plasma levels of leptin, the recently discovered satiety hormone, are associated with adiposity in humans. OBJECTIVE: To determine whether genetic factors or body fat distribution affect the association between leptin levels and obesity. PARTICIPANTS: 23 healthy identical twin pairs (9 male pairs and 14 female pairs, 33 to 59 years of age) who were discordant for obesity (average weight difference, 18 kg). MEASUREMENTS: Fasting plasma leptin levels were measured by radioimmunoassay. Distribution of abdominal fat into visceral and subcutaneous compartments was estimated by use of magnetic resonance imaging. RESULTS: Plasma leptin levels were threefold higher in obese twins than in lean twins (mean +/- SD, 18.7 +/- 12.5 micrograms/L compared with 6.4 +/- 4.8 micrograms/L; P < 0.001); a similar difference was seen when the entire study group was divided according to sex. Compared with lean twins, plasma leptin levels were 3.7-fold higher in the obese twins who had visceral fat accumulation greater than the median and 2.1-fold higher in the obese twins who had visceral fat accumulation less than the median. The intrapair differences in leptin levels correlated with the corresponding differences in percentage of body fat in women (r = 0.73; P = 0.003) but not in men and correlated with differences in visceral fat area in men (r = 0.79; P = 0.019) and women (r = 0.73; P = 0.007). In multiple regression analyses that included intrapair differences in visceral fat area and total body fat, the association between differences in visceral fat area and leptin levels was significant in men (P = 0.029) but not in women. CONCLUSIONS: Plasma leptin levels are increased in obese persons, independent of genetic background. Visceral fat may be of special importance in the regulation of leptin levels, but it is probably less important in women than in men.

Adipose Tissue↗
PubMed1997

Post-marathon paradox in IDDM: unchanged insulin sensitivity in spite of glycogen depletion.

UNLABELLED: Acute physical exercise usually enhances insulin sensitivity. We examined the effect of a competitive 42 km marathon run on glucose uptake and lipid oxidation in 7 runners with insulin-dependent diabetes mellitus (IDDM), aged 36 +/- 3 yr, BMI 23.9 +/- 0.5 kg m-2, VO2max 46 +/- 1 ml kg-1 min-1, HbA1c 7.7 +/- 0.3%, duration of diabetes 16 +/- 5 yr, runtime 3 h 47 +/- 8 min. On the marathon day, they reduced pre-race insulin doses by 26 +/- 8%, and ingested 130 +/- 33 g carbohydrate before, 91 +/- 26 g during, and 115 +/- 20 g after the race. During the run, blood glucose concentration fell from 14.4 +/- 2.0 to 7.4 +/- 3.0 mmol l-1 (p < 0.05) and serum insulin from 51 +/- 8 to 33 +/- 8 pmol l-1 (p < 0.05). Serum NEFA increased by 4-fold (p < 0.05), but fell to the normal level by next morning. Muscle glycogen content was 56% lower (p < 0.05) and glycogen synthase fractional activity 40% greater (p < 0.05) in the morning after the marathon as compared to the resting control day. In spite of glycogen depletion, whole body glucose disposal (euglycaemic insulin clamp) was unchanged, while glucose oxidation (indirect calorimetry) was decreased by 49% (p < 0.05) and lipid oxidation increased by 41% (p < 0.01). There was an inverse correlation between the rates of lipid oxidation and glucose uptake after the marathon (r = -0.75; p < 0.05). IN CONCLUSION: after successfully managed marathon running in patients with IDDM, insulin sensitivity was not increased in spite of low glycogen content and enhanced glycogen synthase activity after marathon, probably because of increased lipid oxidation.

Adult↗
PubMed1997

Occurrence and interrelationships of complications in insulin-dependent diabetes in Finland.

The purpose of the study was to examine the prevalence and interrelationships of micro- and macrovascular complications and their risk factors in insulin-dependent (type 1) diabetic patients. The prevalence of nephropathy, retinopathy and cardiovascular disease was examined and their associations to risk factors (glycemic control, blood pressure, blood lipid concentrations) and neuropathy were estimated in a cross-sectional study. A total of 140 type 1 diabetic patients were examined. They were grouped by gender, age, and duration of diabetes into 14 subgroups of 10 patients each. Nephropathy was observed in 40%, retinopathy in 55%, and signs of cardiovascular disease in less than 5% of patients. Microvascular complications were associated with the duration of diabetes, systolic blood pressure, and serum triglyceride concentration. The glycosylated hemoglobin (HbA1c) level was significantly associated with the presence of nephropathy, whereas the association with retinopathy was of borderline significance. Statistically speaking, the duration of diabetes, mean systolic blood pressure, HbA1c and triglyceride level explained 31% of the variation in log albumin excretion rate (P < 0.001). Duration, age, and triglyceride level explained 46% of the variation in the severity of retinopathy (P < 0.001) and 31% of the variation in the vibration perception threshold in the ankle (P < 0.001). While the well-established risk factors (duration of diabetes, hyperglycemia, and hypertension) are associated with microvascular complications, more than half of the variation in their severity cannot be explained. An additional risk factor may involve triglycerides even at a normal serum concentration. The mechanism could be the incorporation of triglycerides in the cell membrane, leading to variations in membrane fluidity.

Adolescent↗
PubMed1997

The association of acetyl-L-carnitine with glucose and lipid metabolism in human muscle in vivo: the effect of hyperinsulinemia.

We examined whether hyperinsulinemia is associated with changes in the amount of L-carnitine and acetyl-L-carnitine in the muscle and whether the source of acetyl-coenzyme A (CoA) (glucose or free fatty acids [FFAs]) influences its further metabolism to acetyl-L-carnitine or through tricarboxylic acid in the skeletal muscle of man in vivo. Twelve healthy men (aged 45 +/- 2 years; body mass index, 25.2 +/- 1.0 kg/m2) were studied using a 4-hour euglycemic-hyperinsulinemic clamp (1.5 mU/kg/min) and indirect calorimetry. Although the mean muscle free L-carnitine and acetyl-L-carnitine concentrations remained unchanged during hyperinsulinemia in the group as a whole, the individual changes in muscle free L-carnitine and acetyl-L-carnitine concentrations were inversely related (r = -.72, P < .02). The basal level of acetyl-L-carnitine was inversely related to the rate of lipid oxidation (r = -.70, P < .02). In a stepwise linear regression analysis, 77% of the variation in the change of acetyl-L-carnitine concentrations was explained by the basal muscle glycogen level (inversely) and nonoxidative glucose disposal rate (directly) during hyperinsulinemia (P < .001); by adding the final FFA concentration (inverse correlation) to the model, 88% of the variation was explained (P < .001). In conclusion, (1) hyperinsulinemia does not enhance skeletal muscle free L-carnitine or acetyl-L-carnitine concentrations in-man, and (2) the acetyl group of acetyl-L-carnitine in human skeletal muscle in vivo is probably mostly derived from glucose and not through beta-oxidation from fatty acids.

Acetyl Coenzyme A↗
PubMed1997

Leptin and thermogenesis in humans.

We examined changes in serum leptin concentrations and thermogenesis in 12 healthy men (39 +/- 2 years, BMI 22.8 +/- 0.3 kg m-2) during a 4 h euglycaemic hyperinsulinaemia performed on a control day and after a day of competitive marathon runs. As compared with the control day, after the marathon, baseline FFA concentration (543 +/- 0.73 vs. 955 +/- 96 mumol L-1, P < 0.05), lipid oxidation rate (0.8 +/- 0.1 vs. 1.2 +/- 0.1 mg kg-1 min-1, P < 0.01) and energy expenditure (5.2 +/- 0.1 vs. 5.5 +/- 0.1 kJ min-1, P < 0.01) were elevated. Baseline serum leptin concentrations were similar on the control and postexercise days and increased during insulin infusion by 35-45% on both days (P < or = 0.01). Baseline serum leptin concentration correlated directly with serum insulin (r = 0.65, P < 0.05) and cortisol (r = 0.64, P < 0.05), and inversely with serum growth hormone concentration (r = -0.66, P < 0.05). In the postexercise study, the rise in energy expenditure during insulin clamp correlated with serum leptin concentration as determined before (r = 0.61, P < 0.05) or at the end of insulin infusion (r = 0.55, P < 0.05). Thus, in healthy individuals with normal body weight: (1) hyperinsulinaemia increases serum leptin concentrations; (2) a rise in energy expenditure correlates with serum leptin concentration. These data suggest that leptin is involved in the regulation of energy expenditure in humans.

Adult↗
PubMed1997

Exercise increases insulin clearance in healthy man and insulin-dependent diabetes mellitus patients.

Exercise is known to decrease insulin secretion, but the effect on insulin clearance is unclear. We examined the effect of exercise in insulin clearance with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run (n = 14) or 44 h after a 2-h treadmill exercise (n = 14), and in seven insulin-dependent diabetes mellitus (IDDM) patients 12 h after a marathon run, and after a resting, control day. During the post-exercise insulin infusion, steady-state plasma insulin concentration was reduced by 9% in healthy men after both types of exercise, and by 16% in the diabetic subjects compared with the control study (P < 0.05 in all). In healthy men, C-peptide concentrations were more than one-third lower during insulin infusion, both after the marathon run (P < 0.001) or treadmill exercise (P < 0.02) compared with the control study. Insulin clearance was significantly increased by exercise both in healthy men (9% P < 0.05) and in IDDM subjects (15%, P < 0.05). After exercise, endogenous insulin secretion in healthy men is reduced and insulin clearance is enhanced both in healthy men and in IDDM patients. Decreased insulin availability may allow enhanced muscle lipid utilization and spare glucose after long-term exercise.

Adult↗
PubMed1997

Serum leptin concentration and fuel homeostasis in healthy man.

We studied the interrelationship between the obese gene product serum leptin, insulin and counter-regulatory hormone concentrations and glycogen synthesis in 26 healthy men. A 4-h euglycaemic insulin clamp with muscle biopsies was performed after a resting control day in 26 subjects, and in 14 of them also after heavy, glycogen-depleting (32%, P < 0.01) exercise. Serum leptin concentrations were at baseline 34% (0.67 +/- 0.18 vs. 1.03 +/- 0.13 ng L-1, P < 0.05) lower after the exercise, and rose during hyperinsulinaemia by 56% (to 1.38 +/- 0.19 ng L-1, P < 0.001) and 34% (to 1.05 +/- 0.20 ng L-1, P < 0.01) after the post-exercise and control studies respectively. Basal serum leptin concentration correlated positively with body mass index (r = 0.42, P < 0.05), serum cortisol concentration (r = 0.70, P < 0.001) and the rise in muscle glycogen content during the clamp (r = 0.43, P < 0.05) and inversely with serum growth hormone concentration (r = -0.43, P < 0.05). There was a positive correlation between serum leptin after hyperinsulinaemia and serum insulin concentration during the hyperinsulinaemia (r = 0.42, P < 0.05). After exercise, basal serum leptin level correlated with serum triglyceride concentration (r = 0.82, P < 0.001) and after hyperinsulinaemi serum leptin correlated positively with muscle glycogen content (r = 0.56, P < 0.05). It was concluded that serum leptin concentrations correlate directly with serum insulin, cortisol and triglyceride and inversely with growth hormone concentrations. They are decreased by glycogen-depleting exercise and increase during hyperinsulinaemic clamp. These data suggest that leptin is associated with factors regulating fuel homeostasis and its hormonal control in man.

Adult↗
PubMed1997

Metabolic response to lactitol and xylitol in healthy men.

Sugar alcohols are used in food products, yet their metabolic effects in humans are poorly known. We examined plasma glucose, insulin, and C-peptide responses and changes in carbohydrate and lipid oxidation after the ingestion of 25 g lactitol, xylitol, or glucose. Eight healthy, nonobese men were studied after an overnight fast. After the ingestion of lactitol or xylitol, the rise in plasma glucose, insulin, and C-peptide concentrations was less than after the ingestion of glucose (P < 0.02), with no difference between the two polyols. With the glycemic index of glucose as 100, the indexes of xylitol and lactitol were 7 and -1, respectively. A reactive hypoglycemia was observed 3 h after glucose ingestion, but not after the ingestion of sugar alcohols. There were no significant changes in the carbohydrate or lipid oxidation as determined by indirect calorimetry after the ingestion of sugar alcohols. After glucose ingestion, the rise in carbohydrate oxidation was nearly significant (P = 0.07). In conclusion, lactitol and xylitol cause smaller changes than does glucose in plasma glucose and insulin concentrations and thermogenic response. A small hormonal response and the lack of a thermogenic effect may be beneficial when these sugar alcohols are used in food products. The small glucose and insulin responses also suggest that lactitol and xylitol are suitable components of the diet for diabetic patients.

Adult↗