International Journal of Medical and Health Sciences

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1 International Journal of Medical and Health Sciences Journal Home Page: ISSN: Original article Changes In Anthropometric And Lipid Proifle In Healthy Young Offsprings Of Diabetics Are Not Temporally Linked Shobha M.V 1, Ravindra P.N* 2, Deepali A 3 1&3 Assistant professors, 2 Associate professor,department of Physiology,Sri Siddhartha Medical College, Agalokote, Tumkur- Karnataka ABSTRACT Diabetes mellitus (DM) is an emerging public health concern. Offspring s of diabetics are known to express various trait characteristics. In the present study, anthropometric and metabolic parameters among healthy offspring s with (n=50) and without (n=50) family history of type 2 DM is compared. Anthropometric measurements, fasting blood sugar and lipid profile were estimated. Cases showed significant increase in their anthropometric measurements than controls; and they also demonstrated significant increase in total cholesterol, LDL and decreased HDL and HDL/LDL ratio. Cases were further categorized into two subgroups with median BMI (24.39±4.71 kg/m 2 ) as the dividing value (group 1, BMI=21.55±1.73, group 2, BMI=29.03±4.32). Group 2, inspite of showing significant increase in their anthropometric measurements than group1; the lipid profiles were comparable. Thus, demonstrating a temporal dissociation between anthropometric and lipid changes, former preceding the later. Therefore, in younger age group, anthropometric measures could be used for risk stratification and as a metric to evaluate the efficacy of preventive intervention. KEYWORDS: Family history, Type 2 DM, Anthropometric variables, Lipid profile INTRODUCTION Type 2 Diabetes Mellitus (DM) is a raising global health concern. The pathogenesis of type 2 is a complex interplay between genetic, life style and environmental factors, which makes this an interesting and also a complicated issue as far as prevention and management is concerned [1] In India the prevalence is expected to reach 69.9 million by 2025 from the existing 45 million [2]. Studies evaluating among twins and normal population with family history of type 2 DM have shown a preponderance for a genetic basis in the development of insulin resistance and impaired insulin secretion [3]. The life time risk of developing DM is about 3-5 times in offspring s with single parent and 6 times with both the parents having type 2 DM. Off springs with the strong family history, the age of onset of diabetes is known to be much more earlier than their parents [ 4]. According to survey, southern states seem to more vulnerable with having a higher incidence of prediabetic conditions than the northern part of the country [2]. In a population Int J Med Health Sci. January 2013,Vol-2;Issue-1 86

2 survey done in South India, it was noted that 47% of the diabetic patient had first degree family history of diabetes[ 5] Offspring s with family history are known to be more obese, have increased BMI [6,7,8,] and the risk of developing type 2 DM increases fourfold with early onset DM[ 9]. However, Indians are known to exhibit a unique Asian Indian Phenotype characteristic with higher central obesity (WC, WHR) but with lower BMI [2]. There is also clustering of cardiovascular risk factors like, dyslipidemia in the offspring with family history of type 2 DM, which reflects both genetic and environmental factors contributing to the development of the disease [10]. Lipoproteins abnormalities with insulin resistance are commonly reported in this risky group with family history of type 2 DM and these lipid abnormalities is demonstrated even before the development of type 2 DM [11]. Most of the studies evaluating the risk among offspring with family history DM were in the age range of years and are from the western part of the globe [12,13,14]; and a very few studies are conducted among Indian young healthy adults [11]. But, diabetic scenario in India is being unique as mentioned above, the present study attempts to evaluate the risk stratification among healthy young subjects between years age group with family history of diabetes. Therefore anthropometric, blood sugar and lipid profile in young offspring s with family history of type 2 DM is evaluated and compared with their counterparts without family history of type 2 DM. MATERIALS AND METHODS This is a case control study (n=100) with two groups, controls (n=50, male=24. females =26) without family history of type 2 DM and cases (n=50, male=28, females=22) with family history of type 2 DM. All the subjects were healthy, non smokers and non alcoholics. The study protocol was approved by Institutional Ethical Committee. The experimental protocol was explained to the subjects and written informed consent was obtained. Subjects were screened clinically for any acute or chronic medical, psychiatric conditions and on any medications. If subjects were found to be suffering from any disease condition or any medications they were excluded. Subjects were instructed to report to the laboratory with overnight fasting. Anthropometric measurements were carried out with minimal clothing without shoes. Weight in kilograms was measured using standard calibrated balance scale with sensitivity to the nearest 0.1 kg. Height in centimeters was obtained using stadiometer and BMI was calculated using formula weight in kg /height in m square. Waist circumference (WC) in cm was measured at the level of umbilicus after normal expiration in standing position with feet together and arms by the side of the body. Hip circumference (HC) in cm was measured as the maximum girth around the hip. Waist to hip ratio (WHR) was calculated by dividing waist circumference by hip circumference. Waist to height ratio (WHtR) was calculated by dividing waist circumference by height. Venous blood was drawn in sitting posture and serum was separated by centrifugation at 5000 rpm. Fasting blood sugar and lipid parameters was analyzed on the same day. Fasting blood sugar (FBS) was estimated by glucose oxidase method [15]. Total cholesterol (TC), triglyceride (TG) and high density cholesterol (HDL) was assayed by enzymatic calorimetric test by using ERBA diagnostic Mannheim Gmbh kit. Low Density Lipoprotein cholesterol(ldl) was calculated using friedwalds formula LDL = (Total cholesterol HDL) TG/5 [16], since Very Low Density Lipoprotein(VLDL) is the primary triglyceride carrying form in the fasting stage its concentration can be approximated by TG/5. Anthropometric measurements, FBS and lipid profiles were compared between the two groups. Further, the cases were classified into two subgroups based on BMI with median split of 24.49kg/m 2, FBS and lipid profiles were also compared between two subgroups of cases. Int J Med Health Sci. January 2013,Vol-2;Issue-1 87

3 Descriptive statistics is given in mean and SD. Comparison of variables between groups was done using one way Analysis of Variance (ANOVA). p < 0.05 is considered as level of significance. All the statistics was carried out using SPSS version 15. RESULTS This is a case-control study designed to assess the anthropometric and metabolic differences, in offspring s with family history of type 2 DM and without family history of type 2 DM. The mean and SD of anthropometric variables and their comparison between both the groups are depicted in Table. No.1. The subjects of either group were age matched. The average age of controls and cases were 20.58±1.61 and 20.94±1.9 years respectively. The weight of controls was 56.4±9.56 kg and cases was 66±13.9 kg, the difference was significant statistically F= (1,98),18.17, p < Whereas, height between the two groups were comparable (controls =165.4±8.2cm, cases=167.72±7.64cm, F= (1, 98), 1.17, p=0.281). Correspondingly, BMI was significantly more among cases than controls, it was 20.6±2.29kg/m 2 in controls and 24.39±4.71kg/m 2 among cases, F= (1, 98), 25.31, p= WC of controls was 74.32±8.47 cm and cases was 81.2±12.14 cm, which is significantly more in cases (F= (1, 98), 10.79, p=0.001). Whereas, WHR did not showed any significant difference between the two groups (controls=0.81±0.066 cases=0.83±0.058, (F= (1, 98), 2.55, p=0.113). But, WHtR was significantly more among cases compared to controls, the mean values were 0.44±0.04 and 0.48±0.06 respectively among controls and cases, (F= (1, 98), 11.63, p=0.001). Thus, the anthropometric measurements showed more BMI, WC and WHtR among subjects with family history of type 2 DM. Table 1: Comparison of anthropometric parameters between controls and cases Variables Controls (n=50) Cases (n=50) F value p value Age (years) 20.58± ± Weight (kg) 56.4± ± ** Height (cm) 165.4± ± Body Mass Index 20.6± ± ** (BMI) Kg/m 2 Waist Circumference(WC) (cm) Waist Hip Ratio(WHR) Waist Height Ratio(WHtR) 74.32± ± ** 0.81± ± ± ± ** Values are depicted in Mean SD, ANOVA, * p < 0.05,** p<0.001 Int J Med Health Sci. January 2013,Vol-2;Issue-1 88

4 The comparison of metabolic parameters between both the groups is depicted in Table.No.2. Fasting blood sugar did not showed any significant difference between controls and cases (controls = 84.42±4.33mg/dl and cases = 85.6 ±3.67mg/dl (F= (1, 98), 2.086, p=0.152). Total cholesterol was ±17.88 mg/dl and 169.3±25.75mg/dl respectively among controls and cases. The difference was statistically significant (F= (1, 98), p=0.000). Interestingly, HDL was significantly less in cases when compared to controls (controls = 38.22±2.03 and cases = 37.22±1.7 F= (1, 98), p = 0.009). But, LDL was significantly more among cases compared to controls with mean values of 108±24.06mg/dl and 92.84±16.5mg/dl respectively (F= (1, 98), , p=0.000). HDL/LDL ratio was significantly less in subjects with family history of type 2 DM when compared to controls. The HDL/LDL was 0.41±0.066 in controls and 0.36±0.063 in cases (F= (1,98), , p=0. 001). Whereas, triglycerides and VLDL did not showed any significant difference between both the groups. Thus, the lipid parameters showed increased total cholesterol and LDL levels and decreased HDL and HDL/LDL ratio among offspring s of type 2 DM. Table 2: Comparison of Fasting Blood Sugar and lipid parameters between controls and cases. Variables Controls Cases F value p value (n=50) (n=50) Fasting blood sugar (mg/dl) 84.42± ± Total cholesterol (mg/dl) ± ± ** Triglycerides (mg/dl) ± ± HDL (mg/dl) 38.22± ± ** LDL (mg/dl) 92.84± ± ** VLDL (mg/dl) 23.55± ± HDL/LDL ratio 0.41± ± ** Values are depicted in Mean Average BMI of cases was 24.39±4.71 mg/kg 2, which is quite near to overweight value. The minimum value of BMI was 18 mg/kg 2 and maximum was mg/kg 2 encompassing normal to obese range. Therefore cases were further classified into two subgroups based on BMI and their anthropometric and lipid profile were compared. The Median BMI (24.49kg/m 2 ) was considered to split the cases into two subgroups. Group.1 (n=31) average BMI was 21.55±1.73 mg/kg 2 which is in normal range and Group.2 (n=19) average BMI was 29.03±4.32 mg/kg 2 are in overweight range. The difference in SD, ANOVA,* p < 0.05,** p<0.001 their BMI was statistically significant (F = (1, 48) p = 0.000). The comparison of anthropometric and lipid profile between these two groups is depicted in Table.No.3.Weight of the group 1 was 60.83±kg/m 2 and group 2 was 75.94±16.09kg/m 2 the difference was statistically significant but the height was comparable between the two subgroups. WC of group.1 was 75.83±8.82 cm and group.2 was 89.94±11.88 cm, the difference was statistically significant, (F= (1, 48), p=0.000). WHR showed significant difference between group.1 and group.2 with respective mean values 0.816±0.05 and Int J Med Health Sci. January 2013,Vol-2;Issue-1 89

5 0.865±0.05 (F= (1, 48), 9.93, p=0.003). The mean value of WHtR among group 1 was 0.45±0.04 and group 2 showed 0.53±0.06 and the difference was statistically significant (F= (1, 48), 33.60, p=0.000). Therefore, the WC, WHR and WHtR were significantly more among overweight individuals with family history of type 2 DM, when compared to their counterparts who had normal BMI. However, the most surprising and interesting was that the lipid profile which was comparable between both the groups. Table 3: Comparison of Anthropometric and Lipid Parameters between two subgroups among cases Variables Group 1 Group 2 F value p value n =(31) n = (19) Weight (kg) 60.83± ± ** Height (cm) ± ± Body mass index (BMI) (kg/m 2 ) Waist circumference (WC) (cm) Waist hip ratio(whr) Waist height ratio(whtr) Total cholesterol (TC) (mg/dl) Triglycerides (mg/dl) 21.55± ± ** 75.83± ± ** 0.816± ± * 0.45± ± ** 165.1± ± ± ± HDL (mg/dl) 37.8± ± LDL (mg/dl) ± ± VLDL (mg/dl) 24.73± ± HDL/LDL ratio 0.37± ± Values are depicted in Mean In summary, our results have demonstrated that the offspring s with family history of type 2 DM are endowed with more BMI, WC, WHtR, total cholesterol, LDL and less HDL and HDL/LDL ratio when compared to offspring s without family SD, ANOVA, * p < 0.05, ** p<0.001 history of type 2 DM. Cases who were overweight (i.e. Group 2) demonstrated comparable lipid profile than their counterparts with normal weight (i.e. Group 1), Thus, demonstrating that Int J Med Health Sci. January 2013,Vol-2;Issue-1 90

6 anthropometric changes precedes the alteration in lipid profile among youngsters of high risk group. DISCUSSION In the present study the subjects with family history of type 2 DM showed increased BMI, WC, WHtR, total cholesterol, LDL levels and decreased HDL levels and HDL/LDL ratio. The two subgroups of cases which were classified according to BMI, the group with higher BMI naturally had significantly more WC, WHR and WHtR when compared to group with normal BMI. But, the lipid profile was comparable between the two subgroups of cases inspite of significant difference in their BMI and anthropometric measures. In this study, the offspring s with family history weighed more than controls, whereas, the height was comparable. Studies have shown that obesity and family history of type 2 DM are the risk factors for development of type 2 DM [17]. In our study subjects with family history showed higher BMI when compared to controls but this is not in the range to classify as obese in accordance with WHO criteria. However, the BMI > 23 kg/m 2 in Indians is considered to be the higher risk factor for developing DM [18]. Accordingly, the subjects with family history in the present study (BMI =24.39kg/m 2 ) could be considered to be at higher risk to develop DM. Further, there are reproducible evidences to demonstrate that subjects with obesity as indicated by anthropometric measurements like WC, WHtR are also at higher risk to develop type 2 DM [19, 2, 3]. In our study, the determinants of visceral adiposity, i.e WC and WHtR was significantly more in cases than the controls. These determinants are strongly correlated with the development of glucose intolerance, the main eitopathological processe in developing DM [20, 21]. In contrast, few reports have showed that Indians for unique unknown reasons are known to be at higher risk to develop glucose intolerance in spite of low BMI [22]. This unique anthropometric presentation termed as unique Asian phenotype with more WC and low BMI is the characteristic of both native and migrant Indians who are at risk to develop DM. Visceral adiposity is considered to be the major factor favoring development of type2 DM among Indian who are at risk inspite of lower BMI [2]. Considering all these available data, the subjects in the present study with family history of type 2 DM are known to be endowed with high risk physical characteristics that favour to develop type 2 DM. The family history revealed 8% of subjects with both parents being diabetic, 76% reported only father and 16% only mother being diabetic. Further, 38% of both their grandparents were reported to be diabetic, 6% and 8% being grandfather and grandmother diabetic respectively. A follow up study [23] of normal healthy non diabetic men for about 22.5 years has demonstrated that maternal familial history appears to be important risk factor for developing DM. There are contrasting studies carried out among Indian population who have reported that maternal diabetes is the major genetic risk factor to develop type 2 DM [24] and few have reported that maternal history may not be a major risk.[25] However, studies conducted in western population have shown that maternal and paternal diabetes offer a equal risk to transmit diabetes to offspring s [26]. In the present study, even though the percentage of paternal history of diabetes was more than maternal, due to limitation of number of subjects the risk calculation based on parenteral history was not carried out. However, the main objective of the present study was to evaluate the anthropometric and metabolic parameters among young healthy subjects with family history of diabetes mellitus. The subjects with family history in the present study demonstrated altered lipid profile when compared to controls. Total cholesterol, LDL was increased, whereas, HDL and HDL/ LDL ratio was decreased. Increased fat deposition bringing Int J Med Health Sci. January 2013,Vol-2;Issue-1 91

7 about increased BMI and WC is known to be one of the major causative factor for such altered lipid profile that is been observed in our subjects [27]. Further, insulin resistance which may be a genetically inherited trait [28] is also known to enhance lipolytic activity thereby increasing fatty acid levels thus bringing about these altered changes in lipid profile and can also cause dyslipidemia in individuals with normal glucose tolerance [27]. However, not estimating the insulin resistance in the present study forms the great limitation to directly correlate with the observed changes. Yet, with this limitation, the present study offers an important observation that the young healthy individuals with positive family history of diabetes who are euglycemic has shown difference in anthropometric and lipid profile favoring higher risk to develop DM. These measures could be used as the risk stratification tools and also the yard to assess the effectiveness of any preventive intervention. In the process of evaluating the results, it was observed that BMI had a very wide range among subjects with family history. It was ranging between 18kg/m 2 to kg/m 2 (median BMI 24.9kg/m 2 ) ranging from normal BMI to obesity range. This wide range of BMI could be one of the major confounding factors for the observed results in the lipid profile. Therefore, the subjects with family history were further divided into two subgroups by taking median split BMI 24.9kg/m 2. The BMI between these two groups (BMI of group1 = 21.55kg/m 2, BMI of group 2 = 29.03kg/m 2 ) are statistically significant. Therefore, in accordance with cutoff for Asian Indians phenotype i.e. BMI> 23kg/m 2 group 2 are at higher risk of developing type 2 DM. Anthropometric variables (WC, WHR and WHtR) in group 2 were significantly higher than group 1. However, the most interesting and intriguing finding was that the lipid profiles were comparable between these two groups. This is the unexpected but a unique observation of the present study. This observation offers an insight that the changes in anthropometric variables may not be aligned with the changes in lipid profiles. Our observation demonstrates that anthropometric changes could precede the alteration in lipid profile among healthy youngsters of high risk group to develop type 2 DM. There is a report demonstrating similar findings earlier [29]. They demonstrated that the children (10-14 years) with family history of type 2 DM had increased weight, BMI, WC, fasting insulin and HOMA index, but the lipid parameters did not showed any difference between two groups. But when the children s were further categorized according to BMI; obese hypereinsulinemica children showed decreased HDL, increased LDL and increased triglycerides, but, obese and overweight normoinslulenemic children did not demonstrated any changes in lipid profile. Thereby demonstrating that age and insulin levels are the major contributing variables that need to be considered while interpreting results of the risk group. In the present study, when anthropometric and lipid profiles were compared between cases and controls, cases demonstrated significant difference in both; thereby tempting to interpret that a strong family history of diabetes may be a contributing factor for both changes in anthropometric and lipid profiles. However, when cases were further classified based on BMI, there was a temporal delink between anthropometric changes and lipid profile. Therefore, this study gives a glimpse that anthropometric changes precede far earlier than the onset of changes in lipid profile. Inspite of limitations like not evaluating insulin levels, the present preliminary study, can potentially put forth that the anthropometric variables would be a better measures for risk stratification for diabetes among high risk euglycemic younger age group with family history of type 2 DM, and can form a base for further studies. Long term follow up studies of high risk group by evaluating anthropometric, insulin levels and autonomic variables would aid in better understanding the trait effect of genetic inheritance Int J Med Health Sci. January 2013,Vol-2;Issue-1 92

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