leptin and Myotonic-Dystrophy

We discuss the case of a 56-year-old woman who presented with diabetes from the age of 24. The diagnosis of familial partial lipodystrophy was made after the discovery of the lamin A/C gene 20 years later. The diagnosis enabled the detection of a severe cardiac rhythm disorder with the need for an implantable defibrillator. This disease is a rare disorder characterized by an altered body fat repartition, cardiac rhythm anomalies and muscular dystrophy.

Topics: Body Fat Distribution; Diabetes Complications; Diabetes Mellitus; Diagnosis, Differential; Female; Humans; Lamin Type A; Leptin; Lipodystrophy, Familial Partial; Middle Aged; Mutation; Myotonic Dystrophy

To evaluate serum leptin concentration and its relation to metabolic syndrome (MSy) in non-diabetic patients with myotonic dystrophy type 1 (DM1).. This study included 34 DM1 patients, and the same number of healthy subjects matched for age, sex and body mass index (BMI).. DM1 patients had increased BMI and insulin resistance, and increased leptin and insulin concentrations, but the other features of MSy such as diabetes, glucose intolerance and hypertension were not detected in DM1 patients. Serum leptin levels were higher in patients with DM1 than in healthy controls (8.5 +/- 6.6 ng/ml vs 3.6 +/- 2.9 ng/ml in men, and 13.9 +/- 10.0 ng/ml vs 10.9 +/- 6.9 ng/ml in women, respectively). In DM1 patients, leptin levels correlated with BMI, fasting insulin and insulin resistance (HOMA) (P < 0.01).. The leptin overproduction correlated with insulin resistance in DM1 patients but the significance of this finding remains unclear.

Topics: Adult; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Fasting; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Myotonic Dystrophy; Sex Characteristics; Triglycerides

To investigate the leptin and TNF systems in relation to testosterone in insulin resistant myotonic dystrophy (DM1) subjects.. Fasting morning samples and diurnal sampling during 24 h. Forty-two DM1 subjects (20 women and 22 men; age 41.5 (28.5-58.7) y, body mass index (BMI) 23.3 (18.6-29.2) kg/m(2); median and 10th and 90th percentile, respectively). Fifty healthy volunteers (23 women and 27 men; age 42 (27.0-56.9) y, BMI 24.0 (20.7-29.7) kg/m(2)). Nine men with DM1 and nine healthy men participated in diurnal sampling.. Body composition was measured by bioelectric impedance analysis. Circulating levels of leptin, TNF-alpha, TNFR-II, insulin, testosterone and lipids were measured. The number of CTG triplet repeats was analysed.. Basal as well as median 24 h levels of leptin and TNFR-II were significantly increased in DM1 patients, independent of body fat mass. This was associated with higher insulin and lower testosterone levels in DM1 patients. The genetic defect was related to leptin and TNFR-II levels in DM1 patients.. Hyperleptinemia in DM1 is clearly linked to the concomitant hypogonadism. The genetic defect may directly or indirectly contribute to increased leptin levels. Increased exposure of cytokines may contribute to insulin resistance and other hormonal disturbances in DM1.

Topics: Adult; Antigens, CD; Body Composition; Case-Control Studies; Circadian Rhythm; Electric Impedance; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Myotonic Dystrophy; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Testosterone; Tumor Necrosis Factor-alpha

Insulin resistance is an important determinant of circulating leptin concentrations in humans, but its independent contribution on plasma leptin levels are controversial. In the present study, we characterized plasma leptin levels and their regulation in women with 2 different insulin resistance states: type 2 diabetes and myotonic dystrophy disease, and in controls.. We studied 3 groups of women: 21 type 2 diabetic patients, 20 myotonic dystrophic patients and a control group of 20 normoglycemic subjects, matched in age and body mass index. Body composition, fasting glucose and insulin, IGF-I, IGF-binding protein-3 and leptin were studied. Body composition was measured using a bioelectrical impedance analyser. Insulin sensitivity (in percentage) was modeled according to a computer-based homeostasis model assessment model. Data are expressed in mean +/- SEM.. In both groups of patients, glucose concentrations were higher in type 2 diabetic patients than in myotonic dystrophic patients, and insulin concentrations and insulin sensitivity were similar in the 2 groups of patients (82.4 +/- 18.6% in type 2 diabetic patients vs. 69.7 +/- 9.7% in myotonic dystrophic patients, p = 0.2) and lower than in controls. Serum leptin and leptin/fat mass ratio were higher in myotonic dystrophic patients than in type 2 diabetic patients (30 +/- 4.9 ng/ml vs. 17.7 +/- 2.6 ng/ml, p = 0.03 and 2.32 +/- 0.69 ng/ml/kg vs. 1.07 +/- 0.2 ng/ml/kg, p = 0.02, respectively) or those found in controls. In type 2 diabetic patients, leptin concentrations were correlated with body mass index and body fat, and in myotonic dystrophic patients leptin concentrations were correlated with age, body mass index, fasting insulin and lower insulin sensitivity, whereas leptin concentrations were not correlated with body fat.. These findings suggest that leptin concentrations and regulation in myotonic dystrophic patients are different from type 2 diabetes.

Topics: Adult; Blood Glucose; Body Composition; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Leptin; Middle Aged; Myotonic Dystrophy

Myotonic dystrophy (MyD) is a systemic disorder in which insulin resistance is well recognized. In the present study we have characterized plasma leptin levels in patients with MyD and in age, sex and body mass index (BMI) matched controls and assessed the influence of leptin on the clinical manifestations of MyD.. Body composition, plasma leptin, fasting and post-oral glucose tolerance test insulin, IGF-I and IGFBP3 were studied in 34 MyD patients and 33 controls.. Body composition was measured using a bioelectrical impedance analyzer, and circulating levels of insulin, leptin, IGF-I, IGFBP3 were measured by IRMA or RIA. Insulin sensitivity was modelled according to a homeostasis model assessment (HOMA) computer-solved model.. Percentage body fat was higher in patients than in controls (25.6 +/- 2.28% vs 18.8 +/- 1.53%, P = 0.013). Insulin levels, both fasting and after oral glucose were higher in patients than in controls, and insulin sensitivity was lower in patients than in controls. Serum leptin was higher in patients than in controls (20.98 +/- 3.11 micrograms/l vs 10.4 +/- 1.31 micrograms/l, P = 0.004), and higher in women than in men, both in patients and in controls. In patients, leptin levels were correlated with age, BMI, fasting insulin, insulin area under curve and lower insulin sensitivity, whereas leptin levels were not correlated with body fat or other parameters of body composition. In controls, leptin levels were correlated with BMI and body fat. The results were evaluated using logistic regression models for each of the 2 populations. In the model of MyD, insulin resistance and age correctly identified higher leptin levels in relation to controls out of 87.88% of patients, and in the model of controls male sex with a negative correlation and BMI correctly identified their leptin levels out of 84.33% cases.. These findings show that MyD provides a different model of leptin regulation in humans, and suggest that in MyD patients there are correlations between leptin and insulin resistance and age, irrespective of body fat. In contrast, leptin levels in controls, correlate with sex and BMI. The data on leptin in this population of patients can not be related aetiologically to the muscle disease itself.

Topics: Adolescent; Adult; Aged; Body Composition; Case-Control Studies; Female; Glucose Tolerance Test; Humans; Immunoradiometric Assay; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Logistic Models; Male; Middle Aged; Myotonic Dystrophy; Protein Biosynthesis; Proteins

A 54-years-old woman diagnosed of myotonic dystrophy (MyD) with past medical history of massive postpartum haemorrhage at age 28 and panhypopituitarism was studied. BMI and body composition were determined and we determined baseline serum IGF-I, IGFBP3, insulin and leptin levels and after the IGF-I generation test performed after the GH administration of 0.1 U/kg/day s.c each evening for 4 days. As expected the patient had lower baseline IGF-I and IGFBP3 with high insulin and leptin levels. After IGF-I generation test, IGF-I, IGFBP3 and insulin levels increases without changes in body composition and leptin levels. In the current study, high leptin baseline levels may reflect the hyperinsulinism action over the adipose tissue in MyD and the effect of hypopituitarism over leptin regulation. After 4 days of GH administration, we demonstrated the lack of a modulatory role on leptin levels of GH and acute insulin increase, and a direct effect of GH on leptin can be excluded.

Topics: Body Mass Index; Female; Human Growth Hormone; Humans; Hypopituitarism; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Middle Aged; Myotonic Dystrophy