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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher HbA1c (group 2) consumed more calories (73.5 +/- 10.5 kcal/kg/d) versus patients with lower HbA1c (64.2 +/- 8.7 kcal/kg/d). These findings pointed to the unphysiologic nature of injecting a mixture of insulin twice daily. To cover the relatively big lunch meal (40% to 50% of the total caloric intake in the Arab countries) and prevent afternoon hyperglycemia, there is a great tendency to increase NPH dose before breakfast. This, in turn, induces late-morning hypoglycemia and increases appetite and food intake at that time. Multiple regression analysis showed that circulating leptin concentrations (the dependent variable) were best correlated with the mean skinfold thickness (SFT), BMI, and caloric intake/kg/d (together they explained 65% of the variability in leptin concentrations). It appears that oversubstitution by insulin and increased food intake stimulate fat synthesis and subsequently BMI. Increased appetite and BMI contribute to increased leptin secretion and explains the higher leptin levels in undercontrolled diabetic children (higher circulating HbA1c concentrations) who were oversubstituted by insulin.
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PMID:Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control. 1188 62

We have recently shown that leptin, the product of the obese gene, can directly influence T-cell function. In the work presented here, we explored the role of leptin in the development of spontaneous autoimmunity in the nonobese diabetic (NOD) mouse, an animal model for the study of human insulin-dependent diabetes mellitus (type 1 diabetes). We found that expression of serum leptin increased soon before the onset of hyperglycemia and diabetes in susceptible females. A pathogenetic role of leptin was assessed by administering recombinant leptin to young female and male NOD mice. Intraperitoneal injections of leptin accelerated autoimmune destruction of insulin-producing beta-cells and significantly increased interferon-gamma production in peripheral T-cells. These findings indicate that leptin can favor proinflammatory cell responses and directly influence development of autoimmune disease mediated by Th1 responses.
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PMID:Leptin accelerates autoimmune diabetes in female NOD mice. 1197 30

Leptin is the protein product of the obese (ob) gene, a lipostatic hormone that contributes to body weight regulation through suppressing appetite and/or stimulating energy expenditure in humans and/or rodents. In humans, serum leptin concentrations are increased in relation to increased body fat content. Studies have shown a higher leptin level in women compared with men. However, the gender influence on serum leptin concentrations has never been evaluated in patients with type 1 diabetes. In this study, serum leptin levels and percentage body fat mass were measured in men and women with type 1 diabetes. Fasting serum leptin levels were higher in women (16.7 + 11.6 ng/mL) than in men (3.0 +/- 1.5 ng/mL; P < 0.05) and were independent of exogenous insulin intake and of glucose control. Percentage body fat and fat mass were significant determinants of leptin concentration, whereas age and duration of diabetes were not related to leptin concentration. Subgroups of men (n = 12) and women (n = 11) with total body fat between 20 and 30% were compared. Leptin levels were also higher in women compared with men (13.5 +/- 8.3 ng/mL versus 3.2 +/- 1.7 ng/mL; P < 0.05, respectively). In conclusion, our findings indicate that gender is an important determinant of serum leptin concentration in type 1 diabetics, this gender difference is partly explained by body fat distribution and that type 1 diabetic women may be more resistant than type 1 diabetic men to leptin's alleged lipostatic actions.
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PMID:Higher serum leptin level in women than in men with type 1 diabetes. 1200 76

Over the last 50 years the prognosis for growth and pubertal development in children with type 1 diabetes mellitus (T1DM) has improved considerably. The early reports of Mauriac's syndrome were related not only to relative deficiency of insulin but also reduced caloric intake. Improved insulin delivery and liberalisation of caloric intake has resulted in improved growth, but subtle abnormalities persist. The frequently reported increased height at diagnosis may relate to prior hyperinsulinaemia and genetic background with respect to lDDM2 the insulin gene VNTR. Subsequent growth faltering is thought to be related to impairment of the GH/IGF-1 axis but children with T1DM are also more at risk of hypothyroidism and coeliac disease. At puberty, persisting abnormalities of the GH/IGF-1 axis and our inability to reverse these totally, even with intensified insulin therapy, contribute to the blunted pubertal growth in the girls but abnormal sex steroid concentrations may also be important. Intensification of insulin therapy may result in leptin resistance and excessive gains in fat mass, particularly in girls. Although it is likely that most children with T1DM will have normal final heights, this excessive weight gain in girls may lead to problems with compliance. Furthermore, hyperinsulinaemia in these subjects may also lead to ovarian hyperandrogenism, increased early risk of microvascular complications and long-term risk of cardiovascular disease.
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PMID:Growth and body composition in type 1 diabetes mellitus. 1237 17

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.
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PMID:Leptin levels in children with insulin dependent diabetes mellitus. 1240 31

Leptin, a protein released from adipose tissue, is being recognized to play an integral role in endocrine regulation of metabolism. While it is clearly evident that leptin is decreased during caloric restriction, the response of leptin to other types of stress has been plagued by conflicting data. With hypoglycemia stress, the literature may conflict because experimentally hypoglycemia is induced with infusion of insulin, an endocrine factor that can increase leptin levels. With exercise, leptin's response may depend on duration and intensity of exercise. While it has been clearly shown that the sympathetic nervous system (SNS) inhibits leptin secretion in a variety of experimental modes, the hypothalamic-pituitary-adrenal (HPA) axis may stimulate leptin secretion. This creates a paradox of leptin regulation during stress since both systems are activated with stress. If the SNS inhibition overrides the HPA axis' activation of leptin secretion, leptin's role during stress may be to allow a shifting of fuel consumption towards carbohydrate utilization. In type 1 diabetes mellitus, autonomic dysfunction may prevent the fall in leptin during stress. Although obesity is associated with type 2 diabetes mellitus, patients may have decreased leptin levels, especially when glucose is poorly controlled. This may contribute to further obesity and worsening of the disease. The purpose of this review to is critically analyze the literature regarding the impact of different types of stress on leptin secretion, the function of leptin during stress, and the role of leptin in the pathophysiology of diabetes.
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PMID:Leptin: metabolic control and regulation. 1261 78

Maternal diabetes during pregnancy is associated with excess fetal growth and increased fetal insulin production. We hypothesized that insulin propeptides (proinsulin and 32-33 split proinsulin) might be more robust indicators of chronic fetal overproduction of insulin. We examined insulin-like molecules in cord blood (ILM) (insulin, proinsulin, and 32-33 split proinsulin) in relation to birth weight, maternal glycemia, and cord glucose in 140 offspring of mothers with type 1 diabetes (ODM) and 49 offspring of mothers who did not have diabetes (CONTROL) as well as degradation of ILM in response to sampling conditions at birth. Insulin propeptides were abundant in cord blood, comprising 50% of ILM in CONTROL and 36% in ODM (P < 0.0001) and more resistant to degradation than insulin (P < 0.05). Concentrations of all three ILM were highly intercorrelated with median values 2- to 5-fold higher in ODM than CONTROL [e.g. median (range): insulin ODM 110 (60-217) pmol/liter; CONTROL 22 (15-37) pmol/liter; P < 0.0001]. In ODM, 32-33 split proinsulin and proinsulin were more closely related to birth weight (Spearman r for ILM: r(32-33 split)= 0.54; r(PROINSULIN): r = 0.54; r(INSULIN) = 0.40: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) and fetal leptin (r(32-33 split)= 0.55; r(PROINSULIN); r = 0.54; r(INSULIN) = 0.22: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) than insulin). By contrast, insulin was more closely related to cord glucose (r(32-33 split) = 0.15; r(PROINSULIN): r = 0.10; r(INSULIN) = 0.42: r(INSULIN) > r(32-33 split) and r(PROINSULIN)P < 0.05). In CONTROL, 32-33 split proinsulin was also more closely related to fetal leptin r(32-33 split)= 0.61; r(PROINSULIN): r = 0.29; r(INSULIN) = 0.33: r(32-33 split) > r(INSULIN)P < 0.05). In ODM, 32-33 split proinsulin and proinsulin have closer relationships to fetal growth and leptin concentrations at birth than insulin. Measurement of insulin propeptides may be advantageous in assessment of the influence of maternal hyperglycemia on the newborn.
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PMID:Insulin and insulin propeptides at birth in offspring of diabetic mothers. 1267 54

It has been assumed that the uptake of long chain fatty acids (LCFAs) into skeletal muscle and the heart muscle, as well as other tissues, occurred via passive diffusion. In recent years our work has shown that the LCFA uptake into skeletal muscle is a highly regulated process. The use of giant sarcolemmal vesicles obtained from skeletal muscle and heart has been used to demonstrate that LCFA uptake into these tissues occurs via a protein-mediated mechanism involving the 40 kDa plasma membrane associated fatty acid binding protein (FABPpm) and the 88 kDa fatty acid translocase, the homologue of human CD36 (FAT/CD36). Both are ubiquitously expressed proteins and correlate with LCFA uptake into heart and muscle, consistent with the known differences in LCFA metabolism in these tissues. It has recently been found that FAT/CD36 is present in an intracellular (endosomal) compartment from which it can be translocated to the plasma membrane within minutes by muscle contraction and by insulin, to stimulate LCFA uptake. In rodent models of obesity and type 1 diabetes LCFA uptake into heart and muscle is also increased, either by permanently relocating FAT/CD36 to the plasma membrane without altering its expression (obesity) or by increasing the expression of both FAT/CD36 and FABPpm (type 1 diabetes). Chronic leptin treatment decreases LCFA transporters and transport in muscle. Clearly, recent evidence has established that LCFA uptake into heart and muscle is regulated acutely and chronically.
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PMID:Plasmalemmal fatty acid transport is regulated in heart and skeletal muscle by contraction, insulin and leptin, and in obesity and diabetes. 1286 39

These studies examined the effects of hypoglycemia or exercise on leptin levels in 47 (23 women, 24 men) healthy (age 26+/-2 years, body mass index 23+/-0.5 kg.m(-2)) and type 1 diabetes mellitus (T1DM) subjects (age 29+/-2 years, body mass index 27+/-2 kg.m(-2)). In Study 1, healthy and T1DM subjects were exposed to morning and afternoon 120-min hyperinsulinemic hypoglycemic ( approximately 50 mg/dl) or euglycemic ( approximately 90 mg/dl) clamps. In Study 2, healthy subjects were studied during morning and afternoon 90-min exercise bouts at 50% VO(2max). In Study 1, basal levels of leptin were significantly greater in T1DM vs. the healthy subjects (13.8+/-3 vs. 5.4+/-1 ng/dl; P<.05). However, during the last 30 min of morning hypoglycemia, plasma leptin levels significantly decreased from 5.4+/-1 to 4.0+/-1 ng/dl (P<.05) and remained low during afternoon hypoglycemia (4.3+/-1 ng/dl) in healthy but not T1DM subjects. In Study 2, plasma leptin levels did not significantly change during exercise the bout in healthy men, but significantly decreased 3 h after morning exercise, and continued to decrease during afternoon exercise in healthy women (P<.0001). Thus, plasma leptin levels decrease in response to hypoglycemia in healthy but not T1DM subjects. However, T1DM patients do have increased basal leptin levels compared to healthy man. Lastly, there is a marked sexual dimorphism in plasma leptin responses to repeated episodes of exercise.
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PMID:Leptin responses to antecedent exercise and hypoglycemia in healthy and type 1 diabetes mellitus men and women. 1458 73

Growth, development, and maturation of adipose tissue in the fetus can determine both survival at birth as well as having longer term consequences for adult disease. The mitochondrial proteins uncoupling protein (UCP) 1, voltage dependent anion channel (VDAC), and cytochrome c have an important role in cellular energy regulation. Activity of these proteins is particularly important during the transition from fetal to neonatal life when cellular energy requirements are at near maximal rates. The regulation of these proteins by endocrine factors is highly complex and may be dependent on both fetal number and maternal nutrition. The cytokine hormones leptin and prolactin have well established functions in energy regulation and lactation respectively. However, recent data proposes a role in regulation of mitochondrial proteins, particularly UCP1, and thermogenesis. Cortisol is an adrenal hormone with a critical role in fetal tissue maturation, especially the lung. It has now been shown to influence the abundance of UCP1 in the fetus, a role that may in part be regulated by the metabolically active thyroid hormone triiodothyronine. A greater understanding of the regulation of mitochondrial proteins within adipose tissue by endocrine and nutritional factors is likely to be important in preventing neonatal morbidity and mortality. It could also add substantially to our understanding of pathological conditions such as obesity and non-insulin dependent diabetes.
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PMID:Hormonal and nutritional regulation of adipose tissue mitochondrial development and function in the newborn. 1475 65


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