Leptinemia among Obese Omani Adults Newly Diagnosed with Type 2 Diabetes Mellitus: A Case-control Study
Mostafa I. Waly,
Yahya M. Al-Farsi,
Masoud Y. Al-Maskari
Leptinemia is associated with obesity and obesity and hyperinsulinemia are considered as the main etiological factors for type 2 diabetes mellitus (T2DM) among adult subjects. The present case-control study evaluated the dietary pattern and biochemical profile of newly diagnosed T2DM obese Omani adults as compared to their age, weight and gender matched control subjects. Two hundred Omani adults (100 obese adults newly diagnosed with T2DM and 100 healthy controls) were included in this study. Dietary intake, body mass index and biochemical measurements for fasting serum glucose, insulin, leptin and blood glycated hemoglobin levels were evaluated for all study participants. Subjects with T2DM showed significantly (p<0.05) higher daily intake of total fats, carbohydrates and energy as compared to controls. Leptinemia and hyperinsulinemia were common among obese diabetic adults as compared to controls. The mean fasting serum levels of glucose and glycated hemoglobin in obese diabetic subjects were significantly (p<0.05) higher than controls. Serum leptin level was found to be positively correlated with body mass index, serum insulin level and total energy intake in all the study subjects. Our results suggest that leptinemia is a risk factor for T2DM in obese Omani adults.
to cite this article:
Mostafa I. Waly, Amanat Ali, Yahya M. Al-Farsi, Neeru Bhatt, Hashim Al-Kilani, Allal Ouhtit and Masoud Y. Al-Maskari, 2013. Leptinemia among Obese Omani Adults Newly Diagnosed with Type 2 Diabetes Mellitus: A Case-control Study. Journal of Medical Sciences, 13: 208-214.
Received: January 28, 2013;
Accepted: March 16, 2013;
Published: May 17, 2013
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic
hyperglycemia associated with a disturbance of carbohydrate, fat and protein
metabolism resulting from a defect in insulin secretion or action (Samuel
and Shulman, 2012). Sedentary lifestyle, obesity and genetic predisposition
synergize for the global epidemic of T2DM (American Diabetes
Association, 2006). Leptin is an adipocyte-secreted hormone that plays a
key role in regulating the pathophysiology of energy homeostasis, appetite and
obesity (Brennan and Mantzoros, 2006). Leptinemia is
common among obese subjects and serum reflects the amount of energy stored in
adipose tissue (Wauters et al., 2000).
Leptinemia is thought to induce a hyperleptinemic state (leptin resistance)
among obese subjects and it is debatable if obese diabetic adults are resistant
to the effects of leptin in a similar way as the insulin resistance (Mantzoros
et al., 2011; Tasaka et al., 1997).
The ethnic differences in relation to serum leptin level have also been reported,
as the Peruvian and Chilean Indians showed lower serum leptin levels comparing
to the Caucasian population (Perez-Bravo et al.,
1998; Lindgarde et al., 2001). Mexican Americans
have also been reported to have higher serum leptin levels as compared to non-Hispanic
Whites (Wei et al., 1997).
Leptinemia is associated with adiposity in pre-diabetic adults (Al-Daghari
et al., 2006) and the differences in the adiposity features have
been observed between the Asians, Caucasians and other ethnic groups (Thorpe
et al., 2009). It has been suggested that obesity, leptin and insulin
resistance are endogenous factors that might be involved in the etiology of
T2DM among susceptible subjects in a pattern that is different in the Asians
versus Asian-American population (Chan et al., 2009;
McBean et al., 2004).
The Sultanate of Oman has a Middle-Eastern lifestyle with distinct dietary
consumption patterns and is ethnically and culturally different from the Western
countries. There is an accelerated increase in the incidence of T2DM among Omani
adults and T2DM was more prevalent in urban areas than in rural population and
accounted for 12% increase of all newly diagnosed non-communicable diseases
in 2010 (Al-Riyami, 2010; Al-Moosa
et al., 2006). There is no reported data with regard to the assessment
of serum leptin levels in obese Omani adults diagnosed with T2DM. Therefore,
we conducted this case-control study to evaluate the dietary consumption pattern
and leptinemia in normal healthy and newly diagnosed obese Omani adults.
MATERIALS AND METHODS
Study subjects and setting: One hundred Omani adults (newly diagnosed
with T2DM) and one hundred matched controls, non-diabetic normal healthy subjects,
were evaluated from 1st June 2009 to end of June 2010 in the Outpatient Diabetes
Clinic of Sultan Qaboos University Hospital (SQUH), a tertiary referral hospital
and the principal governmental center for T2DM care in Oman. The study protocol
was approved by the Medical Research and Ethical Committee of the College of
Medicine and Health Sciences, Sultan Qaboos University.
Inclusion criteria: All participants were recruited on voluntary basis
and signed an informed consent for the enrollment in the study. Inclusion criteria
were: (1) Non-smokers and non-alcoholics; (2) Free of any endocrine disorders
and non-communicable diseases; (3) Females were neither pregnant nor lactating;
(4) Not receiving any vitamins or nutritional supplements. One hundred cases
(50 male and 50 female subjects) participated in the study. They were all newly
diagnosed with T2DM and did not receive any anti-diabetic medication. The controls
(non-diabetic normal healthy subjects) were randomly selected from those accompanying
the patients or attending the outpatient departments at the SQUH. The controls
were matched with patients based on their age (±5 years), gender ratio
and body weight (±5 kg). Personal interviews were scheduled for all study
participants for completing the study questionnaire.
Anthropometric assessment: Anthropometric measurements (height, weight
and body mass index, BMI) were estimated for all study subjects.
Dietary intake: Dietary assessment was estimated for all study participants.
The retrospective dietary intake of the study participants was estimated using
a semi-quantitative Food Frequency Questionnaire (FFQ), to assess their usual
dietary intake over the previous 6 months (Block et
al., 1990). The portion sizes were determined according to the commonly
used household serving units/measures in Oman. The FFQ was tested for its validity,
reliability and reproducibility before conducting the study. The FFQ included
9 different food groups (breads/cereals, vegetables, fruits, meat/meat substitutes,
milk/dairy products, deserts, beverages, sandwiches and traditional Omani dishes).
The collected dietary intake data was categorized into: (1) Frequency of food
consumption: the number of daily servings of food groups, based on the frequency
of consumption for all the respondents was subsequently grouped according to
Food Guide Pyramid (Van Dijk et al., 2012) and
(2) the daily intake of macronutrients. The Food Processor software version
10.2 (ESHA Research, Salem, OR, USA) was used to calculate the means of daily
nutrient intakes (total energy intake, protein, fats and carbohydrates).
Biochemical measurements: The fasting blood samples were collected at
the Outpatients Clinic of SQUH. They were used for measurements of serum
insulin, leptin and glycated hemoglobin (HbA1c). The diagnosis of T2DM was confirmed
based on Their Fasting Serum Glucose (FSG) values (>7.0 mmol L-1).
Statistical analysis: Data is expressed as Mean±SD (standard
deviation) and was analyzed using The GraphPad Prism statistical software package
for personal computer, version 5. Chi-square (χ2) test was used
for comparing the categorical variables. One way analysis of variance (ANOVA)
followed by Tukey's test, Students unpaired t-test, correlation coefficients
(r) and the stepwise logistic regression analysis were used for comparing the
continuous variables. The p<0.05 was considered as statistically significant.
The general characteristics of the enrolled study participants are presented
in Table 1. Overweight and obesity were prevalent in patients
with T2DM and similar pattern was observed in controls. No significant (p>0.05)
differences were however observed in the Body Mass Index (BMI) of both the cases
and controls. Almost 80% of the cases indicated a family history of T2DM, whereas
only 12-16% of the controls had a family history of T2DM. The average mean Fasting
Serum Glucose (FSG) values in T2DM patients (11.88±0.75 mmol L-1)
were significantly (p<0.05) higher as compared to controls (5.16±0.56
mmol L-1). Similarly the average mean glycated hemoglobin (HbA1c)
values in T2DM patients (11.3±2.2%) were significantly (p<0.05) higher
as compared to controls (5.1±0.6%). The mean fasting serum insulin and
leptin levels were found to be significantly higher in T2DM patients as compared
to controls, t = 11.26 and t = 5.39, respectively, p<0.05 (Fig.
1a and b). In both cases and controls, the serum leptin
level was found to be positively correlated (p<0.05) with BMI (r = 0.695
and r = 0.799, respectively), serum insulin level (r = 0.368 and r = 0.820,
respectively) and total energy intake (r = 0.308 and r = 0.312, respectively).
Table 2 presented the daily servings from different food
groups by the study participants, according to USDA Food Guide Pyramid and data
showed no significant (p>0.05) differences with regard to the consumption
of foods from cereals, meat and meat alternates and milk and milk products groups
between the cases and controls.
|| (a) Hyperinsulinemia and (b) Leptinemia among T2DM patients
||General characteristics of type 2 diabetic patients and controls
|Results are expressed as Means±SD, *p<0.05
|| Food consumption frequency in patients with T2DM and controls
|Results are expressed as Means±SD, *p<0.05
||Average daily macronutrients intake in patients with T2DM
|Results are expressed as Means±SD, *p<0.05
The consumption of fruits and vegetables was however significantly (p<0.05)
higher in controls as compared to T2DM patients. The majority (70%) of T2DM
patients consumed <3 daily servings of vegetables as compared to controls
The data on the average daily macronutrients and energy intake for the study
participants is presented in Table 3. The mean daily intake
of carbohydrates and fats (g day-1) was significantly (p<0.05)
higher in T2DM patients as compared to controls. No significant differences
were however observed in the daily intake of proteins (g day-1) between
the cases and controls. The average daily total energy intake (kcal/day) was
also significantly (p<0.05) higher in T2DM patients as compared to controls.
The model presented in Table 4 shows the association between
the intake of various food items and the risk of type-2 diabetes mellitus. These
associations were determined using the stepwise logistic regression analysis,
where the dependent variables were either the T2DM patients or the controls.
The results indicated that the total fats, saturated fats, sweets and cakes,
red meat and potatoes were the main dietary factors associated with the risk
of T2DM among these study participants.
|| The association of type 2 DM with different categories of
The vegetables and dairy products appeared to be the marginally independent
Our results are the first set of data from Oman that report about the dietary
consumption patterns and their association with the fasting serum glucose, insulin,
leptin and blood glycated hemoglobin levels in normal healthy and newly diagnosed
type-2 diabetic obese Omani adults. In the present study, the mean serum leptin
levels were significantly higher in T2DM patients as compared to controls. The
serum leptin levels were found to be positively correlated with BMI, serum insulin
and total energy intake in both the cases and controls. This indicates a direct
positive correlation between the serum leptin and insulin levels, which is known
to promote the adipogenesis and in turn can be involved in the pathogenesis
of T2DM, this is in agreement with the data from several previous studies, which
reported that the elevated leptin level is a risk factor in the development
of T2DM, in particular in obese diabetic patients (Schmitz
et al., 1997).
Leptin and ghrelin, both released from adipose tissues, modulate the insulin
and glucose metabolism but exert antagonistic effects as the leptin acts to
decrease the appetite and food intake (Zigman et al.,
Leptin crosses the blood-brain barriers through a transport system and acts
on the receptors through the lateral and medial regions of the hypothalamus
to suppress the food intake and stimulate energy expenditure to regulate the
appetite and energy balance (Konukoglu et al., 2006).
Leptin has also a direct effect on insulin release through effects on α-cell
function (Date et al., 2002). Obese subjects
become leptin resistant through a chronic low grade pro-inflammatory state and
high levels of leptin may adversely affect the functioning of α-cells and
eventually can lead to the development of diabetes (Hukshorn
et al., 2004).
Overweight and obesity were prevalent in our study participants as indicated
from high BMI, which was positively correlated with high serum leptin levels
that have also been shown to be directly correlated with total energy intake.
Only a few population-based studies conducted in the Middle-East have reported
an increased consumption of energy-dense high fat and sugar rich fast foods
and decreased intake of fresh vegetables and fruits and their association in
the development of type-2 diabetes mellitus and other non-communicable chronic
diseases in the local population (Musaiger and Miladi, 1997;
In the Sultanate of Oman, the T2DM patients were accounted for 12% of all the
newly diagnosed non-communicable diseases in 2010 (Al-Riyami,
2010). Recently it was reported that the quality of type-2 diabetes management
as indicated by the 3 major intermediate outcome measures (glycemic control,
blood pressure and lipid profile) in the Gulf Cooperation Council (GCC) was
sub-optimal and relatively poor (Alhyas et al., 2011).
In the present study, high daily intakes of carbohydrates, fats and total energy
were prominent among T2DM patients and were significantly (p<0.05) higher
than that of control subjects. The quality of carbohydrates is an important
dietary pattern, which emphasizes that low glycemic index and glycemic load
foods may help to reduce the body weight and may improve the inflammatory and
adipokine profiles in overweight and obese subjects (Neuhouser
et al., 2011). It was also observed that higher intake of sweets
and cakes were common among T2DM patients.
Our results are in line with the findings of previous studies, which reported
that higher intake of simple carbohydrates was associated with hyperglycemia.
The mean daily total fat intake in T2DM patients was significantly higher as
compared to controls. The major sources of dietary fat were from the animal
products mainly containing the saturated fats. The results of our study suggest
that obesity and high daily intake of carbohydrates, fats and total energy are
associated with increased risk of T2DM risk in Oman. Furthermore, our results
are also in line with the data reported in recent studies, which showed that
diets high in glycemic index, glycemic load and starch and low in fibre were
associated with increased risk of diabetes (Bajorek and
Morello, 2010; Sluijs et al., 2010). The
average daily protein intake in T2DM patients and controls was comparable and
was within the normal recommended proportionate percentage daily energy intake
In this study, we observed that the patients with T2DM had low daily intake
of fruits and vegetables, which may be associated with low daily intake of fiber.
Fiber supplementation for T2DM patients can reduce the fasting blood glucose
and HbA1c. This suggests that increasing dietary fiber in the diet of patients
with type-2 diabetes is beneficial and should be encouraged as a disease management
strategy (Post et al., 2012). Dietary fiber
has also been reported to modulate the release of adipokines (adiponectin, leptin,
tumor necrosis factor-α and interleukin-6) that can lead to a chronic sub-inflammatory
state and may play a central role in the development of insulin resistance and
T2DM leading to increased risk of CVD associated with obesity (Sanchez
et al., 2012).
Significantly higher mean fasting serum glucose (FSG) levels and HbA1c values
were observed in T2DM patients as compared to controls. Data suggests that the
foods such as fruits, vegetable, whole grains and legumes, which are rich in
dietary fiber, should be recommended for dietary management of T2DM as they
are considered low glycemic index foods and can help to control the hyperglycemia
in T2DM patients (Bajorek and Morello, 2010). Daily
total vegetable intakes of 200 g or more and green vegetable intake of 70 g
or more has been reported to be well correlated with improved control of HbA1c
and triglyceride levels in elderly type 2 diabetes patients through achieving
a well-balanced diet (Takahashi et al., 2012).
In conclusion, our study suggests that dietary consumption patterns varied,
in particular the intake of carbohydrate, fat and total energy was significantly
higher in newly diagnosed T2DM patients as compared to controls. High serum
leptin levels in T2DM patients were positively correlated with average daily
total energy intake, BMI and serum insulin levels leading to insulin resistance
that might be one of the triggers in the development of T2DM in Omani adults.
The financial support provided through the Sultan Qaboos University Internal
Research Grants (IG/AGR/FOOD/10/01 and IG/AGR/FOOD/11/01) is greatly acknowledged.
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