Zulfania  ( Rehman Medical Institute, Peshawar )
Adnan Khan  ( Rehman Medical Institute, Peshawar )
Tahir Ghaffar  ( Lady Reading Hospital, Peshawar )
Abroo Kainat  ( Rehman Medical Institute, Peshawar )
Maria Arabdin  ( Rehman Medical Institute, Peshawar )
Shafqat Ur Rehman Orakzai  ( Kabir Medical College, Peshawar, PAKISTAN )

Objective: To correlate serum leptin levels in obese and non-obese type 2 diabetic patients and compare them with healthy individuals.

Methods: The case-control study was conducted at the Lady Reading Hospital, Peshawar, and the Rehman Medical College, Peshawar, Pakistan, from June to November 2017, and comprised type 2 diabetic patients and and an equal number of healthy controls. Fasting blood glucose, glycated haemoglobin, serum leptin, and body mass index were assessed in obese and non-obese subjects. Relation between body mass index and serum leptin level was explored. Data was analysed using SPSS 20.

Results: Of the 96 subjects, 48(50%) were in each of the two groups. Among the cases, there were 23(48%) men and 25(52%) women with an overall mean age of 51.27±11.7 years. The control group had 28(58%) men and 20(42%) women with an overall mean age of 49.3±12.1 years. Serum leptin levels were significantly higher in obese 9.42±1.87ng/ml and non-obese 7.21±3.78 ng/ml patients than the controls 5.38±2.20 ng/ml (p<0.05). Serum leptin concentration was significantly correlated with body mass index, fasting blood glucose and BMI, FBG and glycated haemoglobin (p<0.001 each).
Conclusion: Increased levels of serum leptin could be used as a risk factor in the development of type 2 diabetes mellitus.

Keywords: Serum leptin, BMI, Diabetes mellitus. (JPMA 70: 3; 2020).

https://doi.org/10.5455/JPMA.301135

Introduction

In spite of the availability of an effective glycaemic control regime, diabetes mellitus (DM) is still one of the complicated health problems and is an issue of major concern for healthcare providers worldwide¹ and is associated with high risk of developing coronary artery diseases (CADs). ² Leptin is polypeptide protein 16 kDa released from adipocytes, and plays a key role in energy expenditure which helps in the control of bodyweight. ^3,4Leptin plays an important role in regulating appetite and metabolism⁵ whereas obesity promotes a number of cellular processes which lead to weakening of the leptin signalling processes and increases the chances of weight-gain induced by genetic and environmental factors. Normally, leptin reduces bodyweight, and increased blood leptin levels with obesity is an indication of 'leptin resistance'. ⁶Decrease in appetite is indicated by reduced leptin levels. However, in obese people, not only leptin concentration israised but also there is variation among obese people in leptin levels which indicates that the control of synthesis and secretion of leptin may involve other factors than fatty tissues. ⁷Leptin could be the potential and beneficial alternative modality that could be considered with the support of clinical trials for its safety and efficacy⁷ because leptin has a potential role in regulating appetite and can reverse DM by improving glucose tolerance. Although insulin is the main support for the regulation of blood sugar level, it is time to look for alternative therapies for controlling DM. In a study, serum leptin concentration was significantly high in non-insulin-dependent DM patients and the correlation between body mass index (BMI) and leptin concentration with regards to gender was similar⁸ The current study was planned to evaluate the variation in serum leptin levels in obese and non-obese type 2 DM (T2DM) patients and to compare them with healthy controls.

Patients and Methods

The case-control study was conducted at the Endocrinology Department of Lady Reading Hospital (LRH), Peshawar, and the Department of Physiology, Rehman Medical College (RMC), Peshawar, Pakistan, from June to November 2017, and comprised diagnosed T2DM cases of either gender aged 40-60 years with or without diabetic complications. Those excluded were patients with conditions that could affect erythrocyte turnover (haemolysis, blood loss) and haemoglobin variants, patients having acute liver diseases, renal failure and pregnancy, and patients using lipid-lowering drugs, oral contraceptives and hormonal replacement therapy (HRT). The study was approved by the RMC ethics committee, and written informed consent was obtained from all the subjects. All the subjec ts were screened with a detailed questionnaire. Demographic data was collected through a self-administered questionnaire, and BMI was measured independently by using weighing machine and measuring tape. World Health Organisation (WHO) classification for o besity was adopted u sed for BMI purposes.9 Blood samples were collected between 7am and 9am after an overnight fast of 12h. Serum leptin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) kits for human leptin. Fasting blood sugar (FBS) was estimated using glucose oxidase method. The concentration of glycated haemoglobin (HbA1c) was measured immunoturbidimetrically, using a microparticle agglutination inhibition method. In addition to using structure proforma for data collection, document review was done to observe the diagnosis and treatment taken by the patients for diabetes management. Data was analysed using SPSS 20 . Mean±standard deviation (SD) was calculated for numerical variables like age, BMI, serum leptin level, HbA1c levels. Frequencies and percentages were calculated for categorical variables like gender, high leptin levels, and high HbA1c. Chisquare test was used to compare categorical variables like gender, high HbA1C levels and high leptin levels between obese and non-obese diabetic patients while taking p<0.05 as significant. Bivariate Pearson's correlation test was used to see the relationship between BMI and leptin levels in both the groups.

Results

Of the 96 subjects, 48(50%) were in each of the two groups. Among the cases, there were 23(48%) men and 25(52%) women with an overall mean age of 51.27±11.7 years. The control group had 28(58%) men and 20(42%) women with an overall mean age of 49.3±12.1 years (Table 1).



Based on BMI, 12(25%) among the patients were nonobese and 36(75%) were obese. Mean BMI in the patients group was significantly high compared to the controls (p<0.05) (Table 2).



Mean systolic blood pressure (SBP) was 135.4±12.7 mmHg in obese and 130.78±11.4 mmHg in non-obese patients compared to 114.5±10.4 mmHg in the controls. HbA1c was significantly higher in the patients compared to the controls (p<0.05). Mean serum leptin level was significantly higher in obese diabetics 9.42±1.87 compared to the controls 4.87±3.19 (p<0.05). Serum leptin concentration was significantly correlated with BMI, FBS and HbA1c (p<0.001 each) (Table 3).



Discussion

The major finding in the current study was positive  correlation between serum leptin level and HbA1c. Leptin is a vital adipose tissue-derived hormone involved in pathophysiological mechanisms related to DM. The present study showed that serum leptin levels were significantly elevated in obese T2DM patients. The findings are supported by a study which observed that elevated leptin levels could confound an association with diabetes.¹⁰ Another study found that increased levels of serum leptin were associated with increased risk of T2DM. ¹¹ Serum leptin levels were observed to be higher in the obese group and positively correlated with BMI. ¹² Reports regarding the role of leptin in diabetes are inconsistent,  with some studies reporting increased¹³ or decreased¹⁴or unchanged¹⁵ serum leptin levels in diabetics. One study showed that serum leptin was related with diabetes (p=0.001) and highly correlated with waist circumference in obese compared to non-obese diabetics. ¹⁶ The current study observed higher leptin levels in women than in men in both cases and controls. The findings are supported by studies citing various causes of elevated serum leptin levels in women than in men, including high adiposity and subcutaneous fat, existence of a negative correlation between leptin and testosterone levels. ¹⁷ In the current study, HbA1c and FBG was higher in obese diabetics than non-obese diabetics and healthy controls. Analysis intimated that there is relevant affiliation among HbA1C, obesity and lipid distribution in diabetic patients. ¹⁸ The study also showed a positive relationship between insulin resistance (IR) and serum HbA1c levels of obese children. Another study reported no difference between obese and non-obese groups in terms of HbA1c values. ¹⁹ The present study has its limitations. Primarily it is a preliminary study which does not display any effect of medication or time variation on the subjects. Secondly, the sample size is too small to allow any credible inferences. Thirdly, to correspond with leptin levels we did not evaluate / measure fat distribution of the subjects.

Conclusion

There was an association between increased serum leptin levels and T2DM patients. The levels of HbA1c and FBS were high in obese diabetic compared to non-obese diabetics and healthy controls. Higher leptin levels may be considered an additional risk factor in T2DM patients with high BMI.

Disclaimer: None.

Conflict of Interest: None.

Source of Funding: None.

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