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Biomedical subjects

P Ebeling

Publications and source records attributed to P Ebeling.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fatty acid transport protein-1 mRNA expression in skeletal muscle and in adipose tissue in humans.

Fatty acid transporter protein (FATP)-1 mRNA expression was investigated in skeletal muscle and in subcutaneous abdominal adipose tissue of 17 healthy lean, 13 nondiabetic obese, and 16 obese type 2 diabetic subjects. In muscle, FATP-1 mRNA levels were higher in lean women than in lean men (2.2 +/- 0.1 vs. 0.6 +/- 0.2 amol/microg total RNA, P < 0.01). FATP-1 mRNA expression was decreased in skeletal muscle in obese women both in nondiabetic and in type 2 diabetic patients (P < 0.02 vs. lean women in both groups), and in all women there was a negative correlation with basal FATP-1 mRNA level and body mass index (r = -0.74, P < 0.02). In men, FATP-1 mRNA was expressed at similar levels in the three groups both in skeletal muscle (0.6 +/- 0.2, 0.6 +/- 0.2, and 0.8 +/- 0.2 amol/microg total RNA in lean, obese, and type 2 diabetic male subjects) and in adipose tissue (0.9 +/- 0.2 amol/microg total RNA in the 3 groups). Insulin infusion (3 h) reduced FATP-1 mRNA levels in muscle in lean women but not in lean men. Insulin did not affect FATP-1 mRNA expression in skeletal muscle in obese nondiabetic or in type 2 diabetic subjects nor in subcutaneous adipose tissue in any of the three groups. These data show a gender-related difference in the expression of the fatty acid transporter FATP-1 in skeletal muscle of lean individuals and suggest that changes in FATP-1 expression may not contribute to a large extent to the alterations in fatty acid uptake in obesity and/or type 2 diabetes.

Abdomen↗
PubMed2000

Effect of calcitriol on bone loss after cardiac or lung transplantation.

Rapid bone loss after cardiac and lung transplantation results in an increased risk of osteoporotic fracture. This study examined the efficacy of treatment with calcitriol (1,25-dihydroxyvitamin D3) in preventing bone loss in patients undergoing cardiac or lung transplantation. In this 2-year double-blind, stratified study, 65 patients undergoing cardiac or single lung transplantation were randomly allocated to receive either placebo or calcitriol (0.5-0.75 microg/day), the latter for either 12 months or 24 months. All patients received 600 mg calcium/day. Bone mineral density (BMD) was measured every 6 months for 2 years by dual-energy X-ray absorptiometry. There was no significant difference between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporine over the 2 years. Bone loss at the proximal femur was significantly reduced or prevented at all three sites by treatment with calcitriol for 2 years compared with treatment with calcium alone. Treatment with calcitriol for 12 months followed by calcium for 12 months resulted in similar proximal femoral bone loss to that seen in those patients treated with calcium for 24 months, suggesting calcitriol prophylaxis needs to be continued beyond 12 months. At the lumbar spine, there were no significant differences in BMD between groups. Over a period of 2 years, 22 new vertebral fractures/deformities occurred in 4 patients treated with calcium alone compared with one new vertebral fracture in 1 patient treated with calcitriol. Because the sample size was too low to provide reliable interpretation of vertebral fracture rates, this difference is likely a chance result. Mild hypercalcemia was common with calcitriol therapy, as was mild hypercalciuria (59% of patients vs. 10% controls), but there were no significant differences between groups in serum creatinine after 2 years. These data suggest calcitriol has a role in reducing proximal femur bone loss after cardiac or lung transplantation but treatment needs to be continued beyond 1 year.

Adrenal Cortex Hormones↗
PubMed1999

Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes.

AIMS/HYPOTHESIS: Inflammation could play a part in insulin resistance. Thiazolidinediones, new antidiabetic drugs, possess anti-inflammatory effects in vitro. We investigated if acute-phase serum proteins are increased in patients with Type II (non-insulin-dependent) diabetes mellitus who had been treated with insulin and whether troglitazone has anti-inflammatory effects in vivo. METHODS: A total of 27 patients (age 63.0+/-1.7 years, HbA1c 8.8+/-0.3%, BMI 32.7+/-0.8 kg/m2, duration 15.2+/-1.4 years, insulin dose 73.3+/-7.0 U/day) participated in the study. The patients received daily either 400 mg troglitazone or placebo for 16 weeks. Blood samples were taken at baseline, at the end of therapy and after a follow-up time of 23+/-4 days. RESULTS: The concentrations of serum amyloid A (6.2+/-1.1 mg/l) and C-reactive protein (6.1+/-1.1 mg/l) were increased (p < 0.001) and complement protein C3 (1.69+/-0.05 g/l) was also above the reference range for healthy subjects. Placebo treatment had no effect on glucose or inflammation, whereas troglitazone reduced fasting glucose (from 10.4+/-0.6 mmol/l to 8.1+/-0.5 mmol/l, p < 0.01), HbA1c (from 8.7+/-0.3% to 7.5+/-0.3%, p < 0.01), insulin requirements (from 75+/-10 U/day to 63+/-10 U/day, p < 0.05), serum amyloid A (from 6.3+/-1.5 mg/l to 4.0+/-1.3 mg/l, p = 0.001), alpha-1-acid glycoprotein (from 906+/-51 mg/l to 729+/-52 mg/l, p = 0.001) and C3 (from 1.72+/-0.07 g/l to 1.66+/-0.06 g/l, p < 0.05) but not alpha-1-antitrypsin, ceruloplasmin, C-reactive protein or haptoglobin significantly. Concentrations of glucose and acute-phase reactants had returned to those before treatment at the follow-up visit. CONCLUSION/INTERPRETATION: In Type II diabetic patients serum amyloid A and complement protein C3 are raised. Troglitazone exerts a selective reversible action on some acute-phase proteins and C3 but not on others in conjunction with the improvement in glucose metabolism.

Acute-Phase Proteins↗
PubMed1999

Lispro Mix25 insulin as premeal therapy in type 2 diabetic patients.

OBJECTIVE: Insulin Mix25 is a new premixed insulin analog containing 25% insulin lispro and 75% neutral protamine lispro (NPL) suspension (NPL insulin). The aim of the study was to compare serum glucose and insulin responses after breakfast in type 2 diabetic patients who received Mix25, premixed regular/NPH (30%/70%), or NPH insulin before the meal. RESEARCH DESIGN AND METHODS: We studied 22 type 2 diabetic patients of age 62 +/- 1 years, BMI 30 +/- 1 kg/m2, duration of diabetes 15 +/- 2 years, duration of insulin therapy 6 +/- 1 years, insulin dose 65 +/- 6 U/day, and HbA1c 7.9 +/- 0.2%. Ten healthy individuals (age 56 +/- 1 years, BMI 28 +/- 1 kg/m2) served as control subjects. Each patient (except healthy subjects, who were studied once each) was studied three times in a double-blind, randomized fashion. After an overnight fast, the patients received 36 +/- 4 U of test insulin. Ten minutes after insulin injection, the patients ingested a breakfast meal (512 kcal, 60% carbohydrate, 20% fat, and 20% protein), identical in all studies. Blood samples were taken before and at 10- to 30-min intervals for 240 min after the breakfast meal. RESULTS: The peak rise in serum glucose was lower after Mix25 (76 +/- 7 mg/dl) than after 30/70 (94 +/- 5 mg/dl, P < 0.05) or NPH (113 +/- 4 mg/dl, P < 0.005) insulin. The incremental area under the serum glucose curve was 36% smaller after Mix25 than after 30/70 (P < 0.01) and 56% smaller than after NPH (P < 0.005) insulin. The peak rise in serum insulin concentration was higher after Mix25 (103 +/- 18 mU/l) than after 30/70 (87 +/- 13 mU/l, P < 0.05) or NPH (62 +/- 12 mU/l, P < 0.01) insulin. The incremental area under the serum insulin curve was higher after Mix25 than after 30/70 during the first 2-3 h (P < 0.02), but the difference disappeared by the end of the 4-h follow-up period. After Mix25 injection, there was an inverse correlation between the glucose response to a meal and insulin dose (r = -0.56, P < 0.01) or the incremental area under the serum insulin curve (r = -0.39, P < 0.05). No such correlations were observed with the other insulins. CONCLUSIONS: Because of its faster initial absorption rate, the new premixed insulin analog Mix25 reduces blood glucose response to a breakfast meal in type 2 diabetic patients compared with premixed 30/70 (regular/NPH) or NPH insulin.

Blood Glucose↗
PubMed1998

Insulin-independent glucose transport regulates insulin sensitivity.

The glucose transport proteins (GLUT1 and GLUT4) facilitate glucose transport into insulin-sensitive cells. GLUT1 is insulin-independent and is widely distributed in different tissues. GLUT4 is insulin-dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions. We suggest the hypothesis that insulin resistance is dependent on whether glucose is entering through GLUT1 or GLUT4 and on the two functional compartments of glucose 6-phosphate formation within the cell. Glucose entering the muscle cell through GLUT4 and phosphorylated by hexokinase II is mainly directed to glycogen synthesis and glycolysis. If glucose is entering through GLUT1 and phosphorylated by hexokinase I, the glucose 6-phosphate so formed is available for all metabolic pathways, including the hexosamine pathway. Hexosamines have a negative feedback effect on GLUT4, and reduced GLUT4 activity decreases insulin-mediated glucose uptake. Thus, insulin-independent glucose transport through GLUT1 can meet the basal needs of the muscle cell. If glucose entrance through GLUT1 and the activation of the hexosamine pathway is abundant, it can decrease the insulin-mediated glucose transport through GLUT4 leading to insulin resistance.

Animals↗
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

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

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↗
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

Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients.

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, insulin, and testosterone in 15 men with insulin-dependent diabetes mellitus (IDDM; age, 29 +/- 2 yr; body mass index, 22.7 +/- 0.5 kg/m2; body fat, 9.5 +/- 1.0%; insulin dose, 44 +/- 4 U/day; hemoglobin A1c, 8.1 +/- 0.3%; diabetes duration, 12.7 +/- 2.0 yr) and 15 healthy control subjects (age, 27 +/- 1 yr; body mass index, 22.6 +/- 0.4 kg/m2; body fat, 9.6 +/- 0.5%) in the fasting state. In addition, the effect of a 4-h euglycemic hyperinsulinemia (approximately 600 pmol/L) on the plasma leptin concentration was determined. The fasting leptin concentration was negatively correlated to plasma testosterone (r = -0.55; P < 0.05) in IDDM patients. The fasting plasma leptin level rose 25% in healthy subjects (from 1.0 +/- 0.2 to 1.3 +/- 0.3 ng/mL; P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained unchanged (2.7 +/- 0.2 vs. 2.7 +/- 0.2 ng/mL) during hyperinsulinemia. We reached the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is resistant to the acute effect of insulin. 2) Serum testosterone may contribute to the regulation of leptin synthesis in IDDM patients.

Adult↗
PubMed1997

Strategies toward improved control during insulin lispro therapy in IDDM. Importance of basal insulin.

OBJECTIVE: To examine whether overall glycemic control can be improved with insulin lispro by adjustment of the basal insulin regimen without an increased risk of hypoglycemia. RESEARCH DESIGN AND METHODS: A 5-month open study was performed in 66 IDDM patients after they had been transferred from human regular insulin to insulin lispro as a premeal therapy. The premeal and basal insulin regimens were adjusted according to self-monitoring of blood glucose during the visits at 2-week to 1-month intervals. Diurnal glucose profile, hypoglycemic events, HbA1c, and patient satisfaction were evaluated. RESULTS: The mean daily glucose level decreased from 9.2 +/- 0.2 to 8.4 +/- 0.2 mmol/l (P = 0.001) and HbA1c decreased from 8.8 +/- 0.1 to 8.0 +/- 0.1% (P < 0.001) (mean +/- SD). The number of daily NPH injections increased from 1.4 +/- 0.1 at baseline to 3.1 +/- 0.1 at the end of the study. Total daily insulin dose increased by 3 U (7%) because of an 8-U (43%) rise in basal insulin, whereas premeal insulin dose decreased by 5 U (20%). The number of hypoglycemic episodes did not change during the study. Of the patients, 86% considered insulin lispro equal or better than human regular insulin. CONCLUSIONS: Although the study was open, the date suggest that the appropriate combination of insulin lispro and basal insulin can improve postmeal hyperglycemia, HbA1c, and treatment satisfaction without increasing the risk of hypoglycemia.

Adolescent↗