Insulin increases serum leptin concentrations in children and adolescents with newly diagnosed Type I diabetes mellitus with and without ketoacidosis

Abstract

Leptin, the ob gene product [1] is predominantly expressed in white adipose tissue and acts as a signalling factor regulating energy balance through specific receptors located in the central nervous system and in peripheral tissues. Serum leptin concentrations in healthy humans are related to body fat mass, body mass index, sex and pubertal stage. Circulating leptin concentrations decrease in response to short-term fasting in both humans and rodents [2±3] and increase after refeeding or insulin treatment [4±5], also in patients with Type II (non-insulin-dependent) diabetes mellitus [6]. Other than this pulsatile diurnal secretory pattern of leptin related to food intake and insulin secretion or insulin-stimulated glucose metabolism, respectively [7], plasma leptin shows a nocturnal increase. Furthermore, changes in leptin concentrations regulate hypothalamic neuropeptide Y (NPY), which is a potent stimulator of food intake, by negative feedback [8].Bearing in mind the physiological interaction between food intake and insulin secretion, the aim of this study was to analyse the possible impact of insulin concentration on the serum leptin concentration in a group of patients with absent or negligible endo- Diabetologia (1999) Abstract Aims/hypothesis. The aims of this study were to analyse the changes of serum leptin in newly diagnosed children and adolescents with Type I (insulin-dependent) diabetes mellitus after insulin treatment and to examine the possible impact of ketoacidosis on these changes. Methods. Baseline serum leptin concentrations were measured in 28 newly diagnosed Type I diabetic patients [age 8.75 ± 4.05 years (means ± SD); BMI 15.79 ± 2.47 kg/m 2 ; HbA 1 c 11.3 ± 1.9 %] with (n = 18) and without (n = 10) ketoacidosis before commencement of insulin treatment, at the time of diagnosis. Thereafter, during a 4-day course of continuous intravenous insulin injection to gain and maintain euglycaemia, serum leptin concentrations were assessed. Results. Baseline serum leptin concentrations, adjusted to age, BMI, sex and pubertal stage, differed among these patients. There was, however, an increase of leptin in all subjects from 1.37 ± 0.56 ng/ml (mean ± SD) up to 2.97 ± 1.52 ng/ml by 117 % (p < 0.0001) after insulin therapy. On average, peak serum leptin concentration was obtained after 42 h of insulin treatment. Further, there was no difference in the mean increase of serum leptin concentrations in the two groups, namely with and without ketoadicosis, of insulin-dependent diabetic children and adolescents. In addition, there was no correlation between serum leptin concentrations and correction of ketoacidosis during insulin treatment. Conclusions/interpretation. Insulin increases serum leptin, within 1 day, in children and adolescents with newly diagnosed Type I diabetes. Ketoacidosis does not influence this interaction between insulin and leptin. [Diabetologia (1999

Crucial Role of Insulin in Leptin Maintenance. Profound Decrease in Serum Leptin by Octreotide Acetate in Insulinoma Subjects.

“…The present results, together with these data, indicate that circulating leptin is susceptible to decline, presumably dependent on the decrease in serum insulin. In contrast, the prevailing observations from human studies suggest that leptin secretion is rather robust against the acute stimulation by insulin, as mentioned in the introduction [2, [7][8][9]. These characteristics of the relationship between insulin and leptin in humans seem favorable to gain and maintain body fat, together with the well-described "leptin resistance" in obesity.…”

“…This postprandial increase might be attributed to the direct action of insulin, and is thought to participate in regulating food intake and energy expenditure in rodents [1]. In contrast, leptin mRNA expression can be enhanced in human adipocytes only after incubation with insulin for longer than 72 hrs [2,7], and prolonged and supraphysiological insulinemia is necessary to significantly increase serum leptin in healthy subjects [2] and in type 1 diabetic patients with ketoacidosis or ketosis [8,9]. These results suggest that leptin secretion is robust against stimu-lation by insulin in humans.…”

Adiponectin and leptin: Potential tools in the differential diagnosis of pediatric diabetes?

“…Three studies found that leptin was lower in newly diagnosed T1D children compared to healthy controls [94][95][96]. One study reported that leptin concentrations in new onset T1D children were low, normal or high compared to normal standards for age, gender and pubertal stage [93]. Leptin levels increased after initiation of intravenous [93] or subcutaneous [94,96] insulin therapy.…”

“…Only four studies have evaluated serum leptin concentrations in small groups of children and adolescents with newly diagnosed T1D [93][94][95][96]. Three studies found that leptin was lower in newly diagnosed T1D children compared to healthy controls [94][95][96].…”

Leptina e ghrelina na fase aguda e de recuperação da cetoacidose diabética em crianças e adolescentes

“…As concentrações reduzidas de leptina nesse momento são compatíveis em relação aos encontrados por Fluck, Hathout e Kitabchi e concordantes com o fato de a leptinemia ser correspondente ao estado de suficiência de energia e estar diminuída em um momento de hipercatabolismo e hipoinsulinemia. 37,39,40 Os dados, no entanto, são discordantes daqueles encontrados por Nakamura, possivelmente devido aos pacientes avaliados em seu estudo apresentarem sinais de infecção como febre e aumento de proteína C reativa, possivelmente elevando os níveis de citocinas inflamatórias, que poderiam aumentar as concentrações de leptina. Apenas um paciente de nossa casuística apresentou infecção como desencadeante da CAD, porém apresentou também dosagens de leptina com níveis diminuídos no T0 em relação aos apresentados após o início do tratamento, e, portanto, discordante dos dados de Nakamura.…”