Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin in glycemic control in gestational diabetes

1. Introduction

Gestation diabetes mellitus (GDM) is one of the pregnancy adverse conditions with a prevalence of 2–5% [1, 2]. GDM occurs when a pregnant woman who does not have diabetes before pregnancy begins to suffer from high blood sugar level as a result of the pregnancy. GDM has categorized by several scales of intolerance toward glucose intake among pregnant patients. Risk assessment for GDM should undertake at the first prenatal visit. Women with clinical characteristics consistent of a high risk of GDM (marked obesity, personal history of GDM, glycosuria, or a strong family history of diabetes) should undergo glucose testing as soon as feasible. If they are found not to have GDM at that initial screening, they should be retest between 24–28 weeks of gestation. In order to screening of GDM in all pregnant women, fasting glucose, 1 h after oral glucose, 2 h after oral glucose, will be examined in week 24–28 by oral glucose tolerance test (OGGT). In fasting blood sugar test patients fast overnight (at least 8 hours, but not more than 16 hours); however, in OGTT fast patients additionally intake 75gr oral glucose two Hrs. Before taking the blood sample for the test. Elevated blood sugar values in patients indicate that an individual’s body is not able to deal with sugar challenge and they must have diagnosed as a patient with gestational diabetes mellitus. In normal and healthy pregnant women fasting plasma glucose will be reduced, and hyperglycemia after food will appear because of diabetogenic hormones in placenta [3].

Pregnancy complications can be getting worst due to exceeding level of glucose in the bloodstream during pregnancy. Furthermore, GDM will cause multiple health issues in the fetus or newborn babies such as congenital malformation, Abortion, Stillbirth, Macrosomia, Neonatal Hypoglycemia, Hyperbilirubinemia, and Polycythemia [2, 4, 5]. Postprandial hyperglycemia will put the mother’s and baby’s health in a high-risk situation [2, 5]. Thus, it is essential to monitor blood sugar levels to prevent significant and adverse health issues [6].

All women with GDM must have a healthy diet by nutrition consultant and regular exercise programs to prevent overweight and other related health problems [5, 7]. Using medicine is the first option to control blood sugar if diet and exercise are not enough to control blood sugar [5]. Insulin is one of the first therapeutic methods in America which it is recommended to treat GDM.

Aspart Insulin (Novo Nordisk, Novo Rapid, ASP28-Human Insulin) has been approved by the FDA to use in 1999 for the first time in the world. Compare to the regular Insulin, Aspart Insulin has Proline amino acid in position B28 instead of aspartic acid. Furthermore, this product is monomeric and rapid-act [8].

This rapid-acting Insulin is injected subcutaneously exactly before each meal. In compare with regular Insulin, Aspart Insulin has fast effectiveness and short stability in plasma [9]. Levemir is Insulin with long-lasting feature and has more prolonged blood glucose controlling results. Levemir Insulin starts to work within 2–4 hours after injection and stays in blood circulation for 24 hours. Recently, Levemir Insulin approved by FDA and has been used to treat GDM in pregnant women [10].

In this study, we proposed to compare the efficacy of two group insulin which consists of the regular Insulin and NPH (Neutral Protamine Hagedorn) Insulin with Novo-rapid and Levemir to glycemic control in GDM patients.

In a double-blind, randomized clinical trial study, 100 patients with GDM in two group (A & B), (50 in each group) treated, inpatient. In the first group (Group A) patients were treated with regular Insulin with or without NPH, and the other group (Group B) patients treated with Novo-rapid Insulin with or without Levemir Insulin. Subsequent of Insulin administration, patients’ blood sugar checked in fasting, before and one hour after each meal, and also at 12 midnight, and 3 AM. Every time, when glucometer devices checked blood sugar, the dosage of Insulin was measured based on a patient’s demand. The blood glucose levels, the period of hospitalization in the hospital, and patients satisfaction were compared in each group by SPSS21.

3. Results

Both groups underwent evaluation in different variables such as frequency of gestation, previous clinical history, and age of the pregnancy, age of the mothers and their fasting blood sugar level before taking part in this study. By using Mann-Whitney and chi-square analyzing methods, we realized that both groups did not have any significant differences among mentioned parameters and as a result, we could entirely relate the study Results to the type of medicine which we used on patient groups (Table 1).

We have not seen any significant correlation between demographic parameters with the length of the hospitalization period and blood sugar controlling respectively (Table 2).

In order to influence the investigation of different therapeutic methods between two groups on the variation of blood Glucose level at the particular times such as fasting, pre-meal, postprandial, 12 MN, and 3 AM, The Repeated Measure ANOVA method has been used. Then, according to the results, the blood glucose level in patients at most of the measuring times (Fasting, one hour after breakfast, before lunch and after dinner) in both groups were lowered remarkably during the hospitalization period. Nevertheless, we could not find any meaningful differences between the two groups of study ( P value 0.204) and also there are not any significant changes in the glucose level at the time of one hour after lunch ( P value 0.11), before dinner ( P value 0.12), twelve midnight ( P value 0.28), and three AM ( P value 0.08) (Table 3).

According to Table 4, by using the Man-Whitney test, we find out significant differences among patients satisfaction from using two medicine packages. However, the satisfaction rate in group B was higher than group A ( P value 0.038).

Average days of hospitalization along with standard deviation, shortest and most prolonged period of hospitalization, in each group of study are explained in Table 5. Non-parametric Man-Whitney test showed us there are significant differences in hospitalization period between two groups. Average hospitalization days were significantly lower in group B rather than group A ( P value 0.002).

There is no recent study which shows us to prove the effectiveness of two types of mentioned Insulin therapy and also how they could be reliable in controlling blood sugar levels in pregnant women. Similar studies are also limited.

In this study, we tried to eliminate any bias, and we paired patients in several variables such as mother’s age, previous clinical disease, age of the pregnancy, frequency of pregnancy. Moreover, also, the blood sugar level of patients, when they admitted to hospital, were similar between groups.

Consequently, we can note that the results of this study based on the type of medicine and Insulin used on patients. However, there were not any significant differences between the function of Insulin which we used on two study groups.

In a study performed by Pettite and et al. in 2005, fifteen patient’s blood glucose level was monitored, fasting and after a meal, for three days in a row. In that study, the first day there was no Insulin, second-day patients underwent Insulin regular, and third-day Insulin Aspart given to patients. Their study revealed that in two days of Insulin therapy, the blood glucose levels reduced noticeably in patients in comparison with the day whom they did not get any Insulin [11]. This result also supports our data, but according to their short-term study results, the effect of Insulin Aspart on patient’s blood glucose level was better than Regular Insulin. However, in our study which patients followed up in maximum for nine days, the results between two groups of the study did not have any significant differences ( P value 0.20).

In another study [12], 322 women diagnosed with type 1 diabetes who, was pregnant less than ten weeks or were willing to become pregnant, were treated in two groups with Regular and Aspart Insulin. The results showed that Aspart Insulin caused an increase in emerging more term labor newborn in compare with Regular Insulin [12].

Furthermore, in a study [13] which performed on 72 GDM patients in two groups of Aspart Insulin administration and diet controlling, results demonstrate that in case of blood glucose controlling and hypoglycemia, Aspart Insulin efficacy was better than keeping patients on a diet. Also, using Aspart Insulin is efficient and almost safe for GDM patient [13].

Besides, our study’s results showed that using Novo-rapid and Levemir Insulin can control the patient’s blood glucose level as well as Regular and NPH Insulin. One of the crucial points of this study is patient’s satisfaction from using Novo-rapid Insulin in compare with Regular Insulin which it could be due to using Flex pen instead of syringe for injection purpose.

Another remarkable point is the hospitalization period of patients which it was significantly ( P -value 0.002) shorter in Novo-rapid Insulin group in compare with Regular Insulin group. This crucial advantageous point is not only beneficial to patient and physician in case of time-saving during the hospitalization period but also has cost benefits to insurance and health care system.

5. Conclusion

According to this study, we can firmly suggest that using of Novo-rapid and Levemir Insulin compared with Regular and NPH Insulin is more efficient and could give more contentment to patients due to being easy to use among patients and less hospitalization period advantages.

In case of insurance agencies willingness to cover the cost of Novo-rapid and Levemir Insulin as well as the Regular Insulin we suggest the application of Novo-rapid Insulin through the health care system. Because of the favorable aspects of Novo-rapid Insulin, the patient along with the physician and health care system can get several benefits. However, this study and its efficacy warrant further investigations and could give rise to new strategies of therapeutic interventions.