Central Obesity Plays an Important Role for the Development of Type 2 Diabetes in Bangladeshi Women

The number of adults with diabetes in the world increases rapidly than it was expected earlier, In 2004 the number was expected to be 300 million by the year 2025 but in 2011 the number of diabetic people in the World reached 366 million and it again expected to be 552 million by the year 20301. The major part of this numerical increase will occur in developing countries, including Africa1,2,3. Diabetes coexists at greater frequency with dyslipidemia, hypertension, central obesity, and micro-albuminuria, which markedly increase the risk and accelerates the course of atherosclerotic diseases4. World Health Organization (WHO) indicates that in 2005 approximately 1.6 billion adults (aged 15 years and over) were overweight worldwide, while at least 400 mil-


Introduction
The number of adults with diabetes in the world increases rapidly than it was expected earlier, In 2004 the number was expected to be 300 million by the year 2025 but in 2011 the number of diabetic people in the World reached 366 million and it again expected to be 552 million by the year 2030 1 .The major part of this numerical increase will occur in develop-ing countries, including Africa 1,2,3 .Diabetes coexists at greater frequency with dyslipidemia, hypertension, central obesity, and micro-albuminuria, which markedly increase the risk and accelerates the course of atherosclerotic diseases 4 .World Health Organization (WHO) indicates that in 2005 approximately 1.6 billion adults (aged 15 years and over) were overweight worldwide, while at least 400 mil-lion adults were obese.Furthermore, the WHO predicts that by 2015 approximately 2.3 billion adults will be overweight and more than 700 million will be obese 5 .Recent evidence 6 from the non-communicable disease risk factor survey Bangladesh 2010 has shown that 17.6% of the Bangladeshi population are overweight and obesity and noticed that urban population (25.1%) are more prone than rural population (10.2%).Reports on rural Bangladeshi population 7,8 over a 10 year period have shown that the prevalence of diabetes increased from 2.3% in 1999 to 7.9% in 2009.In that study under nutrition, overweight and obesity in 2009 were 14%, 17% and 26% respectively, and the presence of metabolic syndrome (cluster of metabolic risk factors, i.e., insulin resistance, diabetes, obesity indicators, hypertension, hyperlipidemia) according to WHO, IDF (International Diabetes Federation) and ATP III (Adult Treatment Panel III) criteria were 9.9%, 23.7% and 29.6% respectively with the prevalence of overweight and obesity, diabetes and other non-communicable diseases also on the rise.
Excess weight is the most important modifiable risk factor for the development of type 2 diabetes because 85-90% of people with type 2 diabetes are either overweight or obese 9 .The term 'diabesity' has been coined to express that type 2 diabetes is obesitydependent and that obesity is the main aetiological cause of type 2 diabetes 10 .Epidemiological studies have shown that body mass index (BMI) is a powerful predictor of type 2 diabetes 11 .Field et al. reported that both men and women with BMI >35kg/m 2 were approximately 20 times more likely to develop type 2 diabetes compared with normal BMI counterparts 12 .However, obesity is remarkably heterogeneous and some obese patients are insulin-sensitive, and even some massively obese patients show a normal plasma lipoprotein-lipid profile despite their significant excess of body fat 13 .
Waist circumference as a measure of abdominal obesity was proposed as a better predictor of risk of type 2 diabetes development 14 .However, total body fat is not the only source of adverse health complications of obesity; in fact, fat distribution and the relative portion of lipids in various insulin sensitive tissues (skeletal muscle and liver), which affects their normal metabolic pathways, actually determine metabolic risk 15 .Accumulation of intra-abdominal or vis-ceral fat is associated with insulin resistance and is a major feature of metabolic syndrome, which confers a 1.5-2-fold increased risk of developing diabetes and cardiovascular disease (CVD) 16 .
A study on US population have shown that measures of overall and central adiposity were associated with higher circulating levels of TSH and FT 3 in euthyroid adults 17 .Thus, hormonal and metabolic alterations common to central adiposity (e.g., insulin resistance) may influence, or be influenced by, thyroid status.
Insulin resistance is thought to be provoked by visceral obesity due to increased flux of free fatty acids (FFAs) to the liver and increased secretion of inflammatory mediators.It was shown that abdominally obese patients have about 50% increased FFA lipolysis and 50% lower FFA turnover compared with lean individuals 18 .At the same time, abdominally obese patients have a greater FFA lipolysis rate compared with non-abdominally obese patients 18 .
While weight change is largely attributable to an imbalance in energy intake and expenditure 19 , it is also a well recognized and common manifestation of overt thyroid dysfunction due to regulation of resting energy expenditure (REE) by thyroid hormones 20, 21 .Another study has shown that measures of overall and central adiposity were associated with higher circulating levels of TSH and FT 3 in euthyroid adults 17 .To look into this question further, we have investigated type 2 diabetes of Bangladeshi women whether central obesity along with thyroid hormones are associates with the risk of type 2 diabetes.

Subjects and Methods
A total of 60 type 2 diabetic female subjects were selected on the basis of availability from the Out Patient Department (OPD) of BIRDEM and Mitford Hospital, age-and BMI-matched 60 healthy female subjects without family history of diabetes from the friend circles of diabetic subjects were also recruited in this study.Subjects were considered as T2DM using WHO guidelines (fasting serum glucose >6.9 mmol/l and/or 2h serum glucose >11.1mmol/l) 22 .The aim of the study was explained and consent was taken from all the volunteers; clinical examination was done by a registered physician using a predesigned questionnaire.Anthropometric measurements were taken using standard methods.Subjects were requested to come in a prescheduled morning after overnight fasting for the fasting blood sample; subjects were then given 75 gm anhydrous glucose dissolved in 250 ml water.Blood was taken by venepuncture at fasting condition and two hours after glucose loading.Serum was separated through centrifuging for 15 min at 300rpm and stored at -40°C.Serum glucose was measured by glucose-oxidase method and lipid profile by enzymatic colorimetric method using commercial kits (Randox Laboratories Ltd., UK), HbA1c was measured using modified HPLC method (Variant, Bio-Rad, USA).Serum insulin levels were determined by enzyme linked immunosorbent assay (ELISA) method (Linco Research Inc., USA).Serum TSH, T 3 , FT 3 , T 4 and FT 4 concentrations were measured by solid phase, enzyme labeled, chemiluminescent immunometric assay (IMMULITE, DPC).Insulin secretory capacity (HOMA %B) and insulin sensitivity (HOMA %S) were calculated from fasting glucose and fasting insulin using HOMA-CIGMA software 23 .This study protocol was approved by the Ethics Committee of BIRDEM.

Statistical analysis
Statistical analysis was performed using SPSS (Statistical Package for Social Science) software for Windows version 17 (SPSS Inc., Chicago, Illinois, USA).All the data were expressed as mean ±SD (standard deviation), the statistical significance of differences between the values was assessed by unpaired 't' test, binary logistic and multiple linear regression were done among the parameters.A twotailed p value of <0.05 was considered as statistically significant.

Clinical characteristics of the study subjects
Age and BMI of the control (36±5, 25.9±3.1)and diabetic (39±6, 26.4±3.7)subjects were not significantly different.Waist circumference of the control (89±8) subjects was significantly (p=0.046)lower than the diabetic (94±11) subjects.Although hip circumference was not significantly different between the two groups but waist-hip ratio of the control subjects was significantly lower compared to diabetic subjects.Percent body fat content was also not significantly different between the two groups.Although both the systolic and diastolic blood pressure of the two groups were within the normal range but diastolic blood pressure of the control subjects was sig-nificantly lower in control subjects compared to diabetic subjects (table 1).

Biochemical characteristics of the study subjects
Fasting plasma glucose in control and diabetic subjects were 5.3±0.4 and 11.9±5.4.Glycosylated hemoglobin (HbA 1c ) in control and diabetic subjects were 5.8±0.5 and 9.1±2.1.Fasting plasma insulin level in control subjects (7.6±2.2) was significantly (p=0.009)lower compared to diabetic subjects (11.8±9.8).Plasma lipid profile and thyroid hormone status in control and diabetic subjects were not found significantly different (table 2).

Regression analysis
In age-adjusted binary logistic regression analysis, when healthy control subjects were considered as reference group, waist circumference was found to be significantly associated with diabetes (table 3).When serum TSH and waist circumference have been fittrd in a regression curve, TSH have shown positively associated with waist circumference (r=0.398,p=0.005; Figure 1).In multiple linear regression analysis TSH was found to be significantly associated with waist circumference.

Discussion
Obesity is the most important modifiable risk factor in the aetiology of type-2 diabetes mellitus 19,22 .Body mass index (BMI) is the commonest index used to define obesity in clinical practice.However, BMI does not define the presence or absence of central obesity which has been shown to be the most pathogenically important in the aetiology of metabolic disorders.Waist-hip ratio (WHR) has been shown to be a sensitive index of both the total amount of intraabdominal fat as well as the ratio of intra-abdominal to subcutaneous fat ratio 24 .The study done on Nigerian type 2 diabetic patients have shown that BMI is rare, central obesity is quite common 25 .This is crucial in the management of type-2 diabetic patients as central obesity is the form of obesity that is associated with cardiovascular morbidity and mor-tality 26 .This was first highlighted by Vague 27 in 1947 who subsequently re-echoed the same observations nine years later 28 .There is evidence to suggest that visceral adipose tissue is more active metabolically than peripheral adipose tissue and is therefore more deleterious than the latter.For example visceral fat is known to be characterized by increased production of interleukin-6 and tumor necrosis factor-?factors known to be associated with complications of the metabolic syndrome 29 .Obesity occurred more commonly among female patients compared to their male counterparts as shown in the findings of Akintewe and Adetuyibi in Western Nigeria 30 and may be due to cultural practices that tend to limit physical exertion by females with resultant sedentary habits, obesity and its attendant complications.Although the tendency to do outside works have been increasing among the Bangladeshi women but still a large proportion of them are habituated with sedentary lifestyle.Therefore, the present study aims to determine the central obesity in Bangladeshi women whether it played an important role in the development of type 2 diabetes.
In the present study BMI of the control (25.9±3.1) and diabetic (26.4±3.7)subjects was not significantly different.Waist circumference of the control (89±8) subjects was significantly (p=0.046)lower than the diabetic (94±11) subjects.Although hip circumference was not significantly different between the two groups but waist-hip ratio of the control sub-jects was significantly lower compared to diabetic subjects.Percent body fat content was also not significantly different between the two groups.Recently in Southern Ethiopia, Giday et al., have shown that hypertension, central obesity and overweight were found to be significantly associated with risk of having diabetes 31 .Central obesity was found significantly higher in female than male irrespective of having diabetes mellitus, but obesity had no significant difference among both sexes.Abdominal obesity had a graded relationship with diabetes mellitus in both male and females 32 .Abdominal obesity as a clinical feature of excessive accumulation of visceral fat is usually associated with a cluster of cardiovascular risk factors, defined by the WHO as 'metabolic syndrome'.This syndrome is characterized by abdominal obesity, insulin resistance, dyslipidaemia (high

Figure 1 :
Figure 1: Association of serum TSH with waist circumference

Table 1 : Clinical characteristics of the study sub- jects
Central Obesity Plays an Important Role for the Development of Diabetes BMI, Body Mass Index; W_Cir, waist circumference; H_Cir, hip circumference; WHR, waist-hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure

Table 4 :Relationship of waist circumference and Thyroid hormones in type 2 diabetic subjects using multiple linear regression analysis Dependent
Variable: Waist circumference