by Dr. Nibal Abdel Rahman Aboul Ella Clinical Nutrition Department National Nutrition Institute Obesity, Physical inactivity, and Homeostasis Model Assessment (HOMA) as Predictors for Prediabetes among Egyptian Adolescents

Diabetes prevalence is increasing in the developing world due to increased urbanization accompanied by cultural and socio-economic changes. Experts estimated that the number of adults with diabetes will reach 300 million in the year Egypt is expected to rank among the top ten countries for the estimated number of adult with diabetes in the year 2025.

Before people develop type 2 diabetes, they almost always have "pre-diabetes"; blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes. Recent research has shown that some long-term damage to the body, especially the heart and circulatory system, may already be occurring during pre-diabetes. Research has also shown that if an action to manage blood glucose when having pre-diabetes, we can delay or prevent type 2 diabetes from ever developing.

Pre-diabetes is common among obese and is associated with insulin resistance; a state in which normal concentrations of insulin produce a subnormal biologic response. Learning about insulin resistance is the first step to be taken toward making lifestyle changes that will help prevention of diabetes and other health problems.

HOMA (homeostasis model assessment); a computer-solved model, has been used to predict the homeostatic concentrations which arise from varying degrees beta-cell deficiency and insulin resistance. It provides indices of insulin secretion (β) and insulin resistance (R) which derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels.

1.To revise the prevalence of glucose disorders among adolescents, 2.To test for the presence of insulin resistance among those with glucose disorders particularly the obese, 3.To clarify the association between obesity and physical inactivity and dietary fat intake, 4.To test HOMA–R and fasting blood glucose as screening and monitoring tests among adolescents with glucose disorders.

This study is a part of a national Egyptian survey, Diet, nutrition and prevention of chronic non- communicable diseases (DNPCNCD) carried out by teams of National Nutrition Institute. A probabilistic multistage stratified cross-sectional sample representative of preparatory and secondary school students was taken. From Upper Egypt three governorates were randomly chosen (Aswan, Sohag and El-Menia). From Lower Egypt, (Ghariba, Kaliobia, and Kafr El-Shikh) were selected. Giza governorate was chosen instead of Cairo as a metropolitan governorate.

Out of 6018 adolescents, 4251 were assessed by measuring their fasting blood glucose levels. They are the targets of this study. Three types of structured questionnaires (medical, dietary and social) were used to cover topics related to obesity, diabetes, hypertension and physical activity. Studied adolescents were subjected to the following:

1.Medical assessments: including Family history of chronic non-communicable diseases, Pattern of physical activity, symptoms covering various systems, General examination including blood pressure measurements.

2.Dietary assessment: 24 hours recall method obtain accurate amounts of foods & beverages consumed by patients in the 24 hours preceding data collection. Adequacy of the diet consumed was assessed by comparing the energy and nutrient intake of the individual with his recommended dietary allowances "RDA" using FAO and WHO recommendations

3.Anthropometric assessment ; weight, height, waist circumference were measured and BMI was calculated Assessment of BMI for adolescents from years old was done using categories reported by National center for health statistics (NCHS) in collaboration with national center for chronic disease prevention and health promotion (CDC) : - Underweight < 5th percentile - Normal weight 5th - < 85th percentile - Overweight 85th - < 95th percentile - Obese ≥ 95th percentile

Assessment of waist circumference for adolescents from years old was done using categories reported by Fernandez and his co-workers : - wasted < 10th percentile - Normal 10th - < 90th percentile - Obese ≥ 90th percentile

4. Laboratory investigation: Fasting blood glucose Total cholesterol (TC) Triglycerides (TG) HDL-cholesterol LDL-cholesterol Fasting plasma Insulin

5.Statistical Methods: Data Analysis was carried out using SPSS package; version 10. Qualitative data were summarized as percentages and comparison between groups was done using chi square and t-test for proportions. Odds ratio (OR) was used to estimate the relative risk (RR) to have a particular health disorder among the obese adolescents (risky category) in comparison to non-obese (reference category). HOMA-R; a measure of insulin resistance among children and adolescents, is derived from the following equation according to Keskin and his co-workers : HOMA-r = Insulin (μIU/ml /) X fasting glucose (mmol / l) /22.5

ٌ Results of this work show that the prevalence of D.M. among Egyptian adolescents is 0.7% with no age, gender, or area of residence predilections. However, The prevalence in Giza governorate differs significantly from upper and lower Egypt' governorates for reasons that could be related to environmental or life style factors.

Type II diabetes was previously predominant among middle-aged and older people but recently, the age of onset has decreased and it has been reported in adolescents and children worldwide In Egypt the screening for DM in obese adolescents (404 students) revealed the presence of 2 having type II and 3 having impaired fasting glycemia (Ain Shams university).

In recent studies, 5-25% of children with type II diabetes presented with ketoacidosis, and ketonuria was present in a further 33%. The majority of those children will be obese, but the severity of the obesity may be changed by weight loss prior to presentation. These factors may lead to the misclassification of adolescents with type II diabetes as type I, and possibly an under estimation of the current prevalence of this clinical problem

All the 29 known diabetics in the present survey were under-insulin therapy, one was an overweight, and 2 were classified as obese. Whether they are type I or II is going to be assessed and revised by survey management team with subsequent notification for whom it may concern.

Clinical, dietary, and laboratory results in relation to FPG categories showed that the prevalence of high systolic or diastolic blood pressure was more among adolescents with impaired FPG if compared to those with normal FPG. Lipid and lipoprotein patterns did not differ according to FPG categories. Comparing different cutoffs of HOMA-R in relation to FPG categories showed that HOMA-R was higher in prediabetics than those with normal FPG

Normal FBGPre-diabeticsDiabetics % Total No 46.5 (3478) 10.7 (3342) 27.7 (3187) 50.0 (690) 16.6* (668) 36.0* (639) (29) 3.4 (29) 37.0 (27) Table (1): Clinical Criteria in relation to blood glucose Categories: Family history: DM Clinical Data: High SBP High DBP

Table (2): Laboratory Criteria in relation to blood glucose Categories : Normal FBGPre-diabeticsDiabetics % Total No Lipid profile: TC ( > 150 mg /dl) (4) TG ( > 150 mg /dl) (4) LDL-C ( > 130 mg /dl) (4) HDL-C ( <= 35 mg /dl) (4) Fasting insulin level : Low Normal ( μIU/ml) (5) High HOMA-R (>2.5) (6) HOMA-R (>3.16) (6) HOMA-R (>4.0) (6) 7.0 (1442) 7.9 (1739) 7.6 (1543) 9.3 (1721) 6.6 (121) 72.7 (121) 20.7 (121) 67.8 (121) 46.7 (121) 28.0 (121) 7.0 (340) 8.8 (407) 5.6 (360) 7.7 (403) 5.0 (234) 77.4 (234) 17.5 (234) 83.7 * (234) 63.5 * (234) 42.0 * (234) 8.0 (13) 11.0 (18) 12.5 (16) 5.6 (18) (8) 62.5 (8) 37.5 (8) (7)

The present study showed that family history for DM and obesity is more among obese and particularly those with central obesity. The risk for overweight and obese adolescents to have high systolic or diastolic blood pressure, high TC, high TG, or high LDL-c was nearly double that for non-obese and the risk was three times more in presence of central obesity (waist circumference > 90th percentile). Physically inactive adolescents have 1.5 times the risk for obesity and those receiving > 30% of energy from fat have 1.8 the risk for central obesity.

Table (3): Odds Ratio (OR), confidence interval (CI) of obesity indicators in relation to medical and physical inactivity data: Overall adiposity (BMI> 85 percentile) Central Obesity (waist > 90 percentile) OR CI Family history : Obesity DM Clinical data: High SBP High DBP Environmental factors: No physical activity Energy from fat > 30% 1.8 * ( ) 1.6 * ( ) 2.3 * ( ) 2.0* ( ) 1.5* ( ) 1.04 ( ) 3.4* ( ) 2.0* ( ) 3.0* ( ) 2.3* ( ) 1.0 ( ) 1.8 * ( )

Overall adiposity (BMI> 85 percentile) Central Obesity (waist > 90 percentile) OR CI Lipid profile: TC ( > 150 mg /dl) TG ( > 150 mg /dl) LDL-C ( > 130 mg /dl) HDL-C ( > 35 mg /dl) Fasting blood glucose (FBG) HOMA-R (>2.5) HOMA-R (>3.16) HOMA-R (>4.0) 1.9* ( ) 2.0* ( ) 1.9* ( ) 1.2 ( ) 0.95 ( ) 2.97* ( ) 1.87 * ( ) 2.2 * ( ) 3.2* ( ) 2.7* ( ) 2.6* ( ) 1.7 ( ) 0.9 ( ) 1.9 ( ) 1.8 ( ) 0.9 ( ) Table (3): Odds Ratio (OR), confidence interval (CI) of obesity indicators in relation to laboratory data:

People who are overweight, but do not have excessive fat around the abdomen seem less susceptible to health problems than overweight people with central obesity. This latter presents a greater risk to heart disease, early atherosclerosis, hyperinsulinemia, and hyperlipidemia.

Physical training improves insulin sensitivity by increasing insulin dependent glucose transporter GLUT-4 expression in muscle. Furthermore, physical inactivity leads to an increased prevalence of obesity.

Table (5): Sensitivity, specificity and predictive powers of FBG and HOMA-R in relation to dyslipidemia (a condition commonly associating insulin resistance) Laboratory Test Sensitivity (%) Specificity (%) PV of normal test (%) PV of abnormal test (%) FBG: TC TG LDL-C HDL-C HOMA-R: TC TG LDL-C HDL-C

Sensitivity: the power of the test to diagnose the presences of a health disorder among cases truly having the disorder Specificity: the power of the test to exclude the presences of a health disorder among persons not having the disorder Predictive Value of normal test = No of adolescents who had no dyslipidemia and had normal value of the laboratory test (Negative Predictive Value NPV) Predictive Value of abnormal test= No of adolescents who had dyslipidemia and had abnormal value of the laboratory test (Positive Predictive Value PPV).

Sensitivity, specificity and predictive powers of FBG and HOMA-R in relation to triglyrides

Although long term studies have shown that 10% of young people with pre-diabetes will eventually decompensate to overt diabetes, yet lifestyle changes reduced the risk of diabetes by 58% and many people with pre-diabetes returned to normal blood glucose levels. Criteria for considering screening for type 2 DM among adolescents are those recommended by American diabetes association ; overweight with any two of the following: positive family history for DM, signs of insulin resistance or conditions associated with insulin resistance as acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovarian syndrome (PCOs). Age of initiation is at 10 years or at the onset of early puberty. Frequency of screening is every 1-2 years and the test preferred is fasting plasma glucose as it is the most simple, accepted by young and can be used at population-based level.

Type 2 DM in young is serious in terms of morbidity and mortality suggesting that it may be appropriate target for screening. School-based programs promoting healthy eating and increasing physical activity are recommended for prevention of obesity. Major governmental actions that focus on lifestyle will be required. Hypertension and dyslipidemia are common among obese adolescents and require active intervention to postpone long term cardiovascular complications. Population-based prevalence studies among adolescents are still urgent for proper detection, diagnosis, and management strategies.