|Year : 2018 | Volume
| Issue : 2 | Page : 71-74
Insulin resistance profile of apparently healthy term neonates in Lagos, Nigeria
Ibironke J Akinola1, Elizabeth E Oyenusi2, Olatunde A Odusote1, Abiola O Oduwole2, Fidelis O Njokanma3
1 Department of Paediatrics, Lagos State University Teaching Hospital, Lagos, Nigeria
2 Department of Paediatrics, College of Medicine, Lagos University Teaching Hospital, Lagos, Nigeria
3 Department of Paediatrics and Child Health, Lagos State University College of Medicine, Lagos, Nigeria
|Date of Web Publication||10-Apr-2018|
Dr. Ibironke J Akinola
Department of Paediatrics, Lagos State University Teaching Hospital, Lagos
Source of Support: None, Conflict of Interest: None
Background: While there is currently much emphasis on the developmental origins of diseases associated with deranged metabolism in developed societies, there is a paucity of data on this subject in developing countries. Insulin resistance (IR) at birth is known to be the earliest detectable abnormality in the natural history of diabetes. It is also a precursor of obesity and cardiovascular diseases. Objective: The objective of the study was to determine IR profile in apparently healthy term neonates. Methods: The cross-sectional study involved 33 small for gestational age (SGA), 29 appropriate for gestational age (AGA), and 38 large for gestational age (LGA) healthy neonates <48 h of age. Glucose and insulin samples taken after a shortened fasting time were measured with glucose oxidase and Enzyme-linked immunosorbent assay methods, respectively. Homeostatic model assessment of IR (HOMA-IR) was calculated. Results: The mean fasting glucose, fasting insulin, and HOMA-IR were 2.66 ± 0.7 mmol/L, 8.68 ± 3.63 μU/mL, and 1.01 ± 0.46, respectively. Fasting glucose levels in LGA, AGA, and SGA neonates were 2.92 ± 0.76 mmol/L, 2.58 ± 0.53 mmol/L, and 2.45 ± 0.68 mmol/L, respectively (p = 0.012). Insulin levels of LGA, AGA, and SGA were 9.47 ± 4.77 μU/mL, 8.44 ± 2.03 μU/mL, and 7.98 ± 3.08 μU/mL, respectively (p = 0.207). HOMA-IR of LGA, AGA, and SGA was 1.18 ± 0.54, 0.97 ± 0.32, and 0.86 ± 0.40, respectively (p = 0.01). The correlation coefficient, r, between HOMA-IR and birth weight was 0.72 (p < 0.001) and the correlation coefficient between HOMA-IR of neonates and maternal body mass index (BMI) was 0.51 (p = 0.001). Conclusions: LGA and infants delivered to mothers with higher BMI are at a higher risk of IR and should be screened at birth.
Keywords: Diabetes, homeostatic model assessment of insulin resistance, insulin, neonate, resistance
|How to cite this article:|
Akinola IJ, Oyenusi EE, Odusote OA, Oduwole AO, Njokanma FO. Insulin resistance profile of apparently healthy term neonates in Lagos, Nigeria. J Clin Neonatol 2018;7:71-4
|How to cite this URL:|
Akinola IJ, Oyenusi EE, Odusote OA, Oduwole AO, Njokanma FO. Insulin resistance profile of apparently healthy term neonates in Lagos, Nigeria. J Clin Neonatol [serial online] 2018 [cited 2018 Oct 17];7:71-4. Available from: http://www.jcnonweb.com/text.asp?2018/7/2/71/229664
| Introduction|| |
Insulin resistance (IR) at birth is the earliest detectable abnormality in the natural history of diabetes. There is currently much emphasis on the developmental origins of diseases associated with deranged metabolism such as obesity and diabetes in developed societies. However, there is a paucity of data on this subject in developing countries. IR is a condition in which the tissues are less responsive or sensitive to the metabolic actions of insulin. It is a continuum  which involves a wide range of values in individuals; individuals with high insulin resistance have high values, while those without insulin resistance have low values.
IR plays a key role in the pathogenesis of many disorders including obesity, ovarian hyperandrogenism, and cardiovascular diseases. High birth weight and low birth weight have been documented as risk factors for the development of IR and diabetes in children and adults.,,, High rates of low birth weight deliveries  and increasing rates of high birth weight neonates, especially in developing countries, therefore, are possible reasons for anticipating increased IR and its associations. There are several methods of assessing IR. However, the homeostatic model of assessment-IR (HOMA-IR) is the most widely used method of assessing IR among the pediatric population. The calculation of HOMA-IR is based on a physiologically based structured model and calibrated using β-cell function at 100% and a normal IR of one.
It is, therefore, highly specific and sensitive for measuring IR.
The general aim of the study was to determine the IR profile in apparently healthy term neonates in relation to their weight for gestational age. The objectives were to determine the plasma levels of insulin and glucose and to determine the IR profile in apparently healthy term neonates at 0–48 h of age.
| Methods|| |
Approval for the study was obtained from the Health Research and Ethics Committee of the Lagos State University Teaching Hospital, Ikeja. Informed consent was obtained from the parents of the study participants.
The present study was cross-sectional and carried out in the Department of Obstetrics and Gynaecology of the Lagos State University Teaching Hospital between January and September 2015. One hundred apparently healthy term neonates delivered consecutively, who met the study criteria were recruited into the study. Inclusion criteria were apparently normal term neonates who had a normal temperature, fed well, were not in any respiratory distress and who had no other signs of disease. Neonates with severe congenital anomalies and those whose mothers were ill were excluded from the study. Birth weight was measured using a weighing scale. Neonates were grouped into high birth weight (≥4.0 kg), normal birth weight (2.5–3.9 kg), and low birth weight (<2.5 kg). Estimation of gestational age was done using a combination of the mothers' last menstrual period and the modified Ballard's scoring system. Gestational age by date was accepted within 2 weeks of the date determined by the modified Ballard's score. Size-for-gestational age was determined using growth charts developed by Mokuolu et al. for Nigerian newborns. Thirty-three small for gestational age (SGA), 29 appropriate for gestational age (AGA), and 38 large for gestational age (LGA) neonates were studied. Maternal body mass index (BMI) was computed using the formula: Weight (kg)/height (m 2). Venous blood was drawn from the dorsum of the hands of the neonates 3 h after the last feed and was considered as a shortened fasting time; 1 ml into ethylenediaminetetraacetic acid bottles for plasma insulin assay and 1 ml into fluoride oxalate bottles for plasma glucose estimation. Samples were stored at −20°C until the sample size was complete. Glucose was measured using glucose oxidase method (Biolabo SA, France) while insulin was measured using enzyme-linked immunosorbent assay (Diametra Insulin ELISA kit, Italy).
IR using the homeostatic assessment HOMA-IR was computed. HOMA-IR = fasting plasma insulin (μIU/mL) × fasting plasma glucose (mmol/L)/22.5 where 22.5 is a constant and serves as a normalizing factor that is the product of normal fasting plasma insulin 5 μIU/mL and the normal fasting plasma glucose at 4.5 mmol/L typical of a normal healthy individual.
The data were stored and analyzed with Statistical Package for the Social Sciences (SPSS version 20, Armonk, NY: IBM Corp). Test for normality using Kolmogorov-Wilk was done. Univariate analysis was carried out for all major variables of interest. Independent Student's t-test and analysis of variance were used to compare two and higher than two means, respectively. Pearson correlation was used to analyze linear relationship between variables. Probability (p value) of <0.05 was considered statistically significant at 95% confidence interval.
| Results|| |
Overall, the mean fasting glucose, fasting insulin, and HOMA-IR were 2.66 ± 0.7 mmol/L, 8.68 ± 3.63 μU/mL, and 1.01 ± 0.46, respectively. Fasting glucose levels in LGA, AGA, and SGA neonates were 2.92 ± 0.76 mmol/L, 2.58 ± 0.53 mmol/L, and 2.45 ± 0.68 mmol/L, respectively (p = 0.01). Insulin levels of LGA, AGA, and SGA neonates were 9.47 ± 4.77 μU/mL, 8.44 ± 2.03 μU/mL, and 7.98 ± 3.08 μU/mL, respectively (p = 0.21). HOMA-IR of LGA, AGA, and SGA neonates was 1.18 ± 0.54, 0.97 ± 0.32, and 0.86 ± 0.40, respectively (F = 4.87, p = 0.01). SGA neonates had the least HOMA-IR of 0.86 while LGA neonates had the highest HOMA-IR of 1.18. The HOMA-IR of male and female neonates is shown in [Table 1] (t = 0.36, p = 0.76).
|Table 1: Mean HOMA-IR levels according to gender, birth weight and size-for-gestational age|
Click here to view
The correlation between HOMA-IR of neonates and maternal BMI showed a positively significant relationship (r = 0.51, p < 0.001). [Figure 1] shows the correlation between HOMA-IR of neonates and their birth weight.
Mean HOMA-IR of neonates with a positive family history of diabetes was lower than that of neonates with a negative family history of diabetes, 0.95 ± 0.31 and 1.04 ± 0.50, respectively. However, the difference between them was not statistically significant (t = −0.84, p = 0.40).
| Discussion|| |
The present study provides the IR profile in Nigerian neonates as assessed by HOMA-IR. There are few studies on HOMA-IR in neonates, thus limiting the choices for comparison across reports. The mean HOMA-IR obtained in the present study is one of the lowest of the few available figures ranging in reports from Sweden, Spain, Mexico, and India. Specifically, the mean HOMA-IR was lowest for SGA neonates and highest for LGA neonates with the mean value for AGA neonates falling in between. This pattern is similar to the observations of Yada et al. in India. It is also similar to findings among Mexican neonates  to the extent that LGA neonates had the highest mean HOMA-IR. This pattern is probably a reflection of increased β-cell mass, leading in turn to higher β-cell activity in LGA neonates. This indicates that, irrespective of genetics and race, HOMA-IR has a tendency to be higher in large neonates.
In comparison, the present study found a lower mean HOMA-IR of 1.18 in LGA neonates than 1.56 from the Indian report. It was, however, close to the figure of 1.3 reported by Ahlsson et al. in Sweden. Thus, the observation of relatively higher levels in Indian participants, relatively lower levels in Nigerian participants, and somewhat intermediate levels in Swedish infants. The pattern and explanations may become clearer when evidence accumulates from more studies in various regions.
In the present study, SGA neonates demonstrated lower HOMA-IR than their AGA counterparts. This finding is similar to that by other authors., At face value, the conclusion for this finding would be that SGA neonates have a low risk for the development of IR. This is not necessarily the case, as a longitudinal study had suggested that reversal does occur at a later age with increased IR occurring in the SGA neonates. Similar longitudinal studies in Africa are needed to confirm this trend of change in IR profile of SGA neonates.
In addition, our study found that all LGA neonates had overweight or obese mothers. It also showed a significantly positive correlation between HOMA-IR of neonates and maternal BMI. This finding is similar to the report by earlier workers  of higher BMI in mothers of LGA neonates. Our study also agrees with that of Catalano et al. that neonates delivered to obese mothers have higher IR. The index study, like that of Simental-Mendía et al., did not demonstrate any significance of family history of diabetes. The predisposition to IR in the presence of a positive family history of diabetes may not be present at birth but may appear later in life.
| Conclusion|| |
The data obtained in the present study indicate that IR is higher in heavier neonates. It also shows that larger neonates are more likely to be delivered to mothers with higher BMI, thus putting them at risk of IR at birth. This conclusion may, however, be limited by the small sample size of neonates in the study group. A higher sample size of LGA and SGA neonates is recommended through prospective multicenter studies for further research and confirmation of the findings of this report. A larger sample size of AGA neonates will also be helpful in determining cutoff levels of normal insulin and HOMA-IR as there are currently no universally accepted values. In the meantime, high birth weight and LGA neonates should be screened for IR at birth and carefully monitored so that appropriate interventions to prevent future occurrence of metabolic disease can be instituted.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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