Indian Pediatrics 2003; 40:946-950 

Insulin Resistance and Lipid Profile in the Children of Young Ischemic Parents

Abstract:

Objective: To determine serum levels of insulin, glucose and lipid profile in children of young parents with CAD. Design: Cohort study. Setting: Tertiary care teaching hospital. Methods: Fifty children in the 5-18 years age group of young parents (< 45 years) with CAD, evaluated for fasting blood glucose, insulin and lipid profile compared with children of normal parents in the same age group. Results: Serum total and LDL-Cholesterol, blood sugar and B.P., both systolic and diastolic were significantly higher in test group as compared to controls though there was no significant difference observed for weight and body mass index (BMI) between the two groups. The insulin levels were also significantly high in the test cases.

Key words: Children, Coronary artery disease, Insulin.

Coronary artery disease (CAD) is the most important clinical manifestation of atherosclerosis, which is responsible for a higher incidence, prevalence and mortality in the Asian Indians in the US as compared to the western counterparts(1). Since 1960, life expectancy in India has increased by 20 years, that is up to 61 years of age(2) and from 1960 to 1995, the prevalence of CAD in adults has increased from 3% to 10%, in urban Indians and from 2% to 4% in rural Indians, with women having rates similar to men(3). Although the prevalence of CAD in rural India is half that of urban India, this is still two - fold higher than the overall CAD rates in the US and several fold higher than those in rural China(4). In 1990, there were 783,000 deaths due to CAD in India, which is expected to double by the year 2015(5). Young Indians with CAD have extensive multi- vessel coronary atherosclerosis, which has been associated with obesity, hypertension and also with an emergence of a new metabolic cluster -Insulin resistance syndrome (Syndrome X)(6).

Recently it has become clear that insulin resistance is an independent risk factor for the development of atherosclerosis(7). Syndrome X is a clinico-metabolic cluster consisting of obesity (elevated waist-hip ratio) with hypertension, dyslipidemia and with elevated insulin levels(8). The dyslipidemia demonstrated has 3 major components: elevated total and low-density lipoprotein cholesterol (LDL-C) with small and more dense components and with overproduction of very low density lipoprotein (VLDL), elevated triglycerides and decreased high density lipo-protein cholesterol (HDL-C). Insulin was found to be a weak but positive indicator of CAD in a meta-analysis of prospective population study(9) and was also ratified by the Quebec Cardio-Vascular Study(10). Insulin resistance predicts the onset of diabetes type 2 in a selected genetically transmitted section of population(11), and is independently associated with hypertension (12) and also stimulates the production of prothrombotic factors(13).

This study was designed to investigate the presence of insulin resistance in the offsprings of young parents with CAD in conjunction with lipid profile and other risk factors.

Subjects and Methods

The study material consisted of 50 children (age 5-18 years) of young parents with history of myocardial ischemia/infarction (fathers <45 years of age and mothers <55 years of age) proved by angiography, treadmill test, electrocardiogram and also in presence of enzymes diagnostic of myocardial infarction. The control group also consisted of 50 children of similar age group, of parents less than 45 years of age and with history of atypical chest pain, which proved to be normal on maximal treadmill test.

A detailed family history of cardio-vascular, hepatic or renal disorders and diabetes mellitus was obtained in all. This was followed by a detailed physical examination, anthropometry and other investigations were carried out to exclude systemic illnesses. Blood pressure (systolic and diastolic) was also measured in all.

Processing of Blood Specimens

Blood samples were taken in a fasting state and were processed for estimation of lipid profile and insulin levels. For lipid profile, the blood sample was analysed in the Olympus Auto-Analyzer and Insulin levels were measured by ELISA method using DAKo Kit. The results were statistically analysed by the application of student ‘t’ test and a 5% probability was considered significant.

Results

There were 50 children, each as test cases and controls with a male to female ratio being 3:2. There was no difference in the mean ages of the two groups e.g., 12 ± 4 years and there was no difference in the anthropometric parameters or body mass index (BMI).

Blood Pressure

There was a significant difference in the systolic and diastolic blood pressures of the test cases (SBP-117 ± 14 mm Hg, DBP-79 ± 9 mm Hg) and the controls (SBP-104 ± 8 mm Hg, DBP-69 ± 8 mm Hg) and the difference was more marked in the 10-18 years.

Lipid Profile

Total serum cholesterol estimated were significantly higher in test cases (169.68 ± 37.5 mg%) as compared to controls (149.42 + 28.2 mg%). Similarly, LDL-cholesterol levels were also significantly elevated in the test cases as compared to controls (105.73 ± 36.43 vs 86.52 ± 25.91 mg%). But tri-glycerides and HDL-cholesterol levels did not differ significantly in the two groups, neither was there any significant difference in the other age groups.

Blood Sugar and Insulin Levels

There was an overall increase in the blood sugar levels in the test cases as compared to controls (89.72 ± 13.49 mg% vs 84.36 ± 12.55 mg%) but the insulin levels were found to be significantly elevated in test cases (34.79 ± 16.82 vs 26.47 ± 11.40 µ/U/ml) showing a definite insulin resistance in the older age groups.

Discussion

The prevalence, hospitalization and mortality from CAD in Asian Indians is reported to be three to four times higher than their European and American counterparts and even higher in comparison to other Asians(14). The elevated risk of cardio-vascular disease in patients with diabetes has been established for some time and the insulin resistant phenotype is characterized by elevated levels of plasma insulin, VLDL, triglycerides and free fatty acids.

Table I 

Clinical Characteristics of the Study - Anthropometry & Blood Pressure.

	Test cases		Control
	5-9 years (Mean ± SD)	10- 18years (Mean ±  SD)	5-18years (Mean ± SD)	P value
Age (Years)	7±2	12±4	12±4	0.721
Weight (Kg)	19±5	37±15	33±16	0.263
Z-Score(weight)	–1.69±0.66	–1.54±3.96	–1.55±1.55	0.988
Height (m)	1.17±0.13	1.43±0.23	1.38±0.24	0.304
Z-Score (height)	–1.37±2.25	–0.88±1.59	–1.57±1.59	0.029
BMI (kg/m)	13.92±2.87	17. 18±3.53	16.64±4.24	0.486
Blood Pressure
Systolic (mmHg)	109±13	117±14	104±8	0.000
Diastolic (mmHg)	74±8	79±9	69±8	0.000

 

TABLE II

Metabolic Variables of the Study. 

	Test cases		Controls
Lipid profile	5-9years (Mean ± SD)	10-18 years (Mean ± SD)	5-18 years (Mean ± SD)	P value
Total Cholesterol(mg%)	173.40 ± 57.51	169.68 ± 37.45	149.42 ± 28.20	0.001
LDL-Cholesterol(mg%)	109.26 ± 60.69	105.73 ± 36.43	86.52 ± 25.91	0.003
HDL-Cholesterol(mg%)	41.80 ± 6.36	39.68 ± 6.43	37.46 ± 5.82	0.072
Triglycerides (mg%)	111.70 ± 33.75	121.28 ± 47.99	117.14 ± 38.96	0.637
Blood Sugar (mg%)	94.00 ± 13.31	89.72 ± 13.49	84.36 ± 12.55	0.042
Insulin (µ/U/ml)	21.02 ± 9.41	34.79 ± 16.82	26.47 ± 11.40	0.005

 

The results of the present study show significant elevation of blood pressure, total serum cholesterol, LDL-C and elevated insulin levels in the test cases. Adolescents (10-18 yrs) are specially at "high risk" being vulnerable for adult diseases within a short period of time. There was no significant difference in the weight and body mass index (BMI) of the test cases and controls in the individual age groups.

The findings of Bogalusa Heart Study were similar to the present study, where the mean levels in offsprings of parents with CAD were found to be significantly higher com-pared to normal children(15). In addition a significant difference was detected in the total cholesterol as well as LDL-Cholesterol but there was no difference in triglycerides or HDL-Cholesterol levels.

All these findings are significant in the light of longitudinal observations in children of young adults showing that levels of serum lipids and lipoproteins persist for sometime -tracking of total and LDL-cholesterol and apolipoprotein B(16).

The mechanisms underlying insulin resistance remain incompletely understood but it is clearly promoted by obesity and physical inactivity acting on a background of genetic susceptibility(17). In the present study, no difference was found in the weight and body mass index (BMI) of the test cases and controls and the biochemical parameters were elevated in the adolescent age groups (10-18 years), thereby signifying that it indicates a metabolic alteration superadded on a genetic back-ground. Though both weight and BMI influence insulin resistance and lipid profile, it might be interpreted that family history of premature CAD is probably responsible for a predisposition to the above mentioned meta-bolic syndrome. The National Cholesterol Education Panel III (NCEP ATPIII) recently has suggested a simple definition of meta- bolic syndrome, which includes upper body obesity, high triglyceride levels, low HDL-cholesterol, hypertension and impaired fasting glucose. Individuals who have 3 or more of the components are defined as having the above mentioned metabolic syndrome(18). In the present study, dyslipidemia with elevated insulin levels were present in 42% of test cases in contrast to22% of controls - who can be labelled as those "at risk" where, interventions are indicated.

The prevention Of CAD can be achieved by breaking the link in the chain of events leading on to Atherosclerosis. Interventions should be directed against the identified risk factors, which include obesity, hypertension and dyslipidemia. To counteract obesity and hypertension, balanced diet is needed along-with physical activity in the form of yoga, aerobic exercises and walking.

In conclusion, "insulin resistance syn-drome" may be detected early in life, putting them in the "high risk" group. A higher section of pediatric population should be screened for BMI, lipid profile and insulin levels and those "at risk" followed up.

Contributors: AK designed the project, drafted the manuscript and will act as the guarantor; VP selected the patients, collected the samples and got the tests done; JB was responsible for the biochemical work-up of the project.

Funding: None.

Competing interests: None stated.

Key Message

• Serum cholesterol, blood sugar, blood pressure and insulin level were significantly high in offsprings of young CAD patients. • Insulin Resistance syndrome may be picked up in the adolescent age group and interventions started in those "at risk" .

 References