Association of Serum Leptin with Beta Cell Dysfunction and Insulin
Resistance among Different Subgroups of Prediabetes
Israt Ara Hossain
1*
, Mijanur Rahman Shah
2
, Fatema Jebunnesa
1
, Rahelee Zinnat
1
and Liaquat Ali
1
1
Department of Biochemistry and Cell Biology, Bangladesh University of Health Sciences, Dhaka, Bangladesh
2
Department of Microbiology and Immunology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
*
Corresponding author: Israt Ara Hossain, Department of Biochemistry and Cell Biology, Bangladesh University of Health Sciences, Dhaka, Bangladesh, Tel:
+88-02-9010654, Fax: +88-02-8055312; E-mail: israt.ru84@buhs.ac.bd
Received date: May 03, 2019; Accepted date: June 21, 2019; Published date: June 28, 2019
Copyright: © 2019 Hossain IA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Accumulating evidence indicates that various adipokines released from adipose tissue have been
involved in abnormal insulin signalling in obesity and type 2 diabetes. However, it is not entirely clear whether these
alterations in serum adipocyte concentrations are already present in the prediabetic state. The present study was
designed to test the hypothesis that elevated levels of serum lepin an index of insulin sensitivity is independently
associated with insulinemic indices among different subgroups of prediabetes.
Materials: Under an observational cross-sectional design a total of 116 Control subjects (M/F, 58/58) and 99
prediabetic subjects (55/44) consisting of 49 Impaired Fasting Glucose (IFG) and 50 Impaired Glucose Tolerance
(IGT) were investigated. Serum glucose was measured by glucose-oxidase method. Serum insulin and leptin were
measured by ELISA techniques. Insulin secretory function (HOMA%B), insulin sensitivity (HOMA%S) and
Homeostasis Model Assessment-insulin resistance (HOMA-IR) were calculated from Homeostasis Model
Assessment (HOMA).
Results: Compared to the Control, IFG and IGT subjects had significantly higher levels of serum leptin (ng/mL)
(p<0.001) and HOMA-IR (p=0.001) respectively. However, compared to their Control counterparts, IFG and IGT
subjects had significantly lower levels of HOMA%B (p=0.001) and HOMA%S (p=0.010). On binary logistic
regression analysis, serum leptin [OR (95% CI): 1.074 (1.019-1.131), p=0.007] and reduced HOMA%S [OR (95%
CI): 0.972 (0.950-0.995), p=0.015] were found to be significant determinants of IGT group after adjusting the effects
of WC and TG. In the same analysis, serum leptin [1.109 (1.054-1.167), p<0.001] and reduced HOMA%B [0.966
(0.951-0.981), p<0.001] were found to be significant predictors of IFG group after adjusting the effects of WC and
TG.
Conclusion: Elevated levels of serum leptin may have an association with the state of IFG and IGT of pre-
diabetes and this association, in turn, is mediated by insulin secretory dysfunction and reduced insulin sensitivity
during this disorder.
Keywords: Leptin; Prediabetes; IFG; IGT; HOMA%B; HOMA%S;
HOMA-IR
Introduction
Prediabetes the prior state of type 2 diabetes mellitus is a
hyperglycemic condition that is characterized by Impaired Fasting
Glycaemia (IFG), Impaired Glucose Tolerance (IGT) and combination
of both defects (IFG-IGT) [1]. Prior clinical and epidemiological
studies reveal both insulin resistance and insulin secretory dysfunction
considered as the pathophysiologic determinants of hyperglycemia
among prediabetes [2,3]. Obesity in association with insulin resistance
and the components of metabolic syndrome manifests as the causative
factors of prediabetes [4].
Adipose tissue in addition to its pathological and physiological
action of the body it provides a link between obesity and insulin
resistance where it acts as an active endocrine and paracrine organ,
secreting a large number of biologically active compounds that
involved in the metabolic homeostasis, collectively called adipokines
[5]. Leptin, a 167 amino acid containing adipokine derived from
adipocyte, which under normal physiological conditions regulate
feeding behavior, energy expenditure, adipose tissue mass, facilitate
glucose utilization and alters insulin secretion [6]. It plays a functional
role in glucose homeostasis through its efects on the synthesis of
insulin which also the risk factors for the development of prediabetes.
Leptin inhibits the synthesis of insulin by inhibiting the pre-proinsulin
mRNA expression in β cells. By activation of ATP-sensitive potassium
channels leptin reduces the secretion of insulin from pancreatic β cells
leading to the development of type 2 DM.
Te exact mechanism whereby elevated levels of serum leptin
predispose to prediabetes is still unknown. During obesity, lipotoxicity
occurs in the extrahepatic tissues which in turn suppress the
responsiveness of non-adipose tissues to the insulin thereby inhibiting
the glucose uptake and its subsequent disposal into the hepatocytes. It
was suggested that insulin resistance to leptin in the β-cells during
glucose intolerant state, might prevent the inhibitory efect of leptin on
insulin secretion resulting in hyperinsulinemia, which might exhaust
pancreatic β-cells leading to the development of hyperglycemia.
Journal of Diabetes and Metabolism
Hossain et al., J Diabetes Metab 2019, 10:5
Research Article Open Access
J Diabetes Metab, an open access journal
ISSN: 2155-6156
Volume 10 • Issue 5 • 1000828