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Human Antibodies -1 (2019) 1–5 1

DOI 10.3233/HAB-190385
IOS Press

Comparison between the effect of regular

human insulin and NPH with novo-rapid and
levemir insulin in glycemic control in
gestational diabetes
Fatemeh Ghaed Aminia , Mohammad Hossein Sharbafib , Anahita Fesharkiniaa and
Soraya Saleh Gargaria,∗

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a
Department of Gynecology and Obstetrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
b
Tehran University of Medical Sciences, Tehran, Iran

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Abstract.
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BACKGROUND: Gestational diabetes mellitus (GDM) is one of the prevalent adverse conditions among pregnant women which
needs delicate monitoring and control. GDM is a state in which the pregnant women’s blood glucose level exceeds the normal
range. Our goal was to determine the best therapeutic method to control the blood glucose level among GDM patients by com-
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paring of the efficacy between two Insulin consisting, Novo-rapid + Levemir Insulin and Regular + NPH Insulin.
METHOD: In this double-blind, randomized clinical trial study, we enrolled 100 women with GDM as an inpatient. In group
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A, patients underwent treating with Regular + NPH Insulin, and in group B, patients underwent treating with Novo-rapid +
Levemir Insulin. Patient’s demographic and clinical information gathered by specified several times during the study and analysis
performed by SPSS21.
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RESULTS: Despite significant changes in the two groups patient’s blood glucose levels; we could not find any remarkable dif-
ferences between the two groups. In the case of patient and health care system satisfaction and the length of the hospitalization
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group, B was better than group A.

CONCLUSION: Altogether, The Novo-rapid and Levemir Insulin in comparing with the Regular and NPH Insulin were practi-
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cally advantageous due to the simple using method and short hospitalization period of the patient. Thus, we prefer and suggest
this beneficial method (using Novo-rapid and Levemir Insulin) to reach therapeutic goals.
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Keywords: GDM, insulin regular, insulin novo-rapid, insulin NPH, insulin levemir

1 1. Introduction fer from high blood sugar level as a result of the preg- 6

nancy. GDM has categorized by several scales of intol- 7

2 Gestation diabetes mellitus (GDM) is one of the erance toward glucose intake among pregnant patients. 8

3 pregnancy adverse conditions with a prevalence of 2– Risk assessment for GDM should undertake at the first 9

4 5% [1,2]. GDM occurs when a pregnant woman who prenatal visit. Women with clinical characteristics con- 10

5 does not have diabetes before pregnancy begins to suf- sistent of a high risk of GDM (marked obesity, per- 11

sonal history of GDM, glycosuria, or a strong family 12

history of diabetes) should undergo glucose testing as 13

∗ Correspondingauthor: Soraya Saleh Gargari, Feto-Maternal soon as feasible. If they are found not to have GDM at 14
Unit, Shohadaye Tajrish Hospital, Shahid Beheshti University of
Medical Sciences, Tehran, Iran. E-mail: soraya_saleh2000@yahoo. that initial screening, they should be retest between 24– 15

co.uk. 28 weeks of gestation. In order to screening of GDM 16

ISSN 1093-2607/19/$35.00
c 2019 – IOS Press and the authors. All rights reserved
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2 F.G. Amini et al. / Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin

Table 1
Comparison demographics and baseline parameters between groups
Demographics and Group A Group B P value
baseline parameters N = 50 N = 50
Age (years)
Mean ± sd (min, max) 32.86 ± 4.53 (23, 42) 33.68 ± 4.18 (23, 43) 0.35
Frequency of pregnancy
Multiparous n (%) 30 (60%) 20 (40%) 0.54
Primiparous n (%) 27 (54%) 23 (46%)
Gestational age
First trimester n (%) 11 (22%) 16 (32%)
Second-trimester n (%) 16 (32%) 9 (18%) 0.91
Third-trimester n (%) 23 (46%) 25 (50%)
Education
Less than high school n (%) 30 (60%) 33 (66%)
High school n (%) 15 (30%) 14 (28%) 0.64
College n (%) 5 (10%) 3 (6%)
Body mass index (kg/m2 )

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Mean ± sd 27.4 ± 4.5 27.6 ± 3.6 0.55
History of GDM in last pregnancy

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Yes n (%) 11 (22%) 7 (14%) 0.12
No n (%) 39 (78%) 37 (86%)

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First FBS before treatment
Mean ± sd (mg/dl) 106.7.4 ± 27.22 100.76 ± 16.27 0.42
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17 in all pregnant women, fasting glucose, 1 h after oral trol blood sugar if diet and exercise are not enough to 46
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18 glucose, 2 h after oral glucose, will be examined in control blood sugar [5]. Insulin is one of the first ther- 47

19 week 24–28 by oral glucose tolerance test (OGGT). apeutic methods in America which it is recommended 48
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20 In fasting blood sugar test patients fast overnight (at to treat GDM. 49

21 least 8 hours, but not more than 16 hours); however, Aspart Insulin (Novo Nordisk, Novo Rapid, ASP28- 50

Human Insulin) has been approved by the FDA to use

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22 in OGTT fast patients additionally intake 75gr oral
23 glucose two Hrs. Before taking the blood sample for in 1999 for the first time in the world. Compare to the 52

the test. Elevated blood sugar values in patients indi- regular Insulin, Aspart Insulin has Proline amino acid 53
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in position B28 instead of aspartic acid. Furthermore, 54
25 cate that an individual’s body is not able to deal with
this product is monomeric and rapid-act [8].
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26 sugar challenge and they must have diagnosed as a pa-
This rapid-acting Insulin is injected subcutaneously 56
27 tient with gestational diabetes mellitus. In normal and exactly before each meal. In compare with regular In- 57
healthy pregnant women fasting plasma glucose will
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sulin, Aspart Insulin has fast effectiveness and short 58
29 be reduced, and hyperglycemia after food will appear stability in plasma [9]. Levemir is Insulin with long- 59
because of diabetogenic hormones in placenta [3].
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lasting feature and has more prolonged blood glu- 60
31 Pregnancy complications can be getting worst due cose controlling results. Levemir Insulin starts to work 61
32 to exceeding level of glucose in the bloodstream dur- within 2–4 hours after injection and stays in blood cir- 62

33 ing pregnancy. Furthermore, GDM will cause multiple culation for 24 hours. Recently, Levemir Insulin ap- 63

34 health issues in the fetus or newborn babies such as proved by FDA and has been used to treat GDM in 64

35 congenital malformation, Abortion, Stillbirth, Macro- pregnant women [10]. 65

36 somia, Neonatal Hypoglycemia, Hyperbilirubinemia, In this study, we proposed to compare the efficacy of 66

37 and Polycythemia [2,4,5]. Postprandial hyperglycemia two group insulin which consists of the regular Insulin 67

38 will put the mother’s and baby’s health in a high-risk and NPH (Neutral Protamine Hagedorn) Insulin with 68

39 situation [2,5]. Thus, it is essential to monitor blood Novo-rapid and Levemir to glycemic control in GDM 69

40 sugar levels to prevent significant and adverse health patients. 70

41 issues [6].
42 All women with GDM must have a healthy diet 2. Material and method 71
43 by nutrition consultant and regular exercise programs
44 to prevent overweight and other related health prob- In a double-blind, randomized clinical trial study, 72

45 lems [5,7]. Using medicine is the first option to con- 100 patients with GDM in two group (A & B), (50 in 73
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F.G. Amini et al. / Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin 3

Table 2 Table 4
Correlation between demographic parameters with the length of hos- The satisfaction rate of participants in each group of study
pitalization and Blood sugar controlling in patients
Level of Treated group P value
Demographic Length of Blood sugar satisfaction Group A (%) Group B (%)
parameters hospitalization control Bad 0.0% 0.0%
P value P value Fine 24.0% 6.0%
Age 0.08 0.14 Good 40.0% 44.0%
Frequency of pregnancy 0.16 0.34 Great 36.0% 50.0% 0.038
Gestational age 0.23 0.76
Education 0.14 0.19
Table 5
Body mass index 0.25 0.11
Comparison of average hospitalization period (days) between two
History of GDM in last 0.18 0.20
groups
pregnancy
Treated Length of hospitalization P value
Table 3 group Mean SD Low High
Comparison of patients’ blood glucose level, before and after the Group A 5.26 2.00 2 days 8 days
intervention Group B 3.98 1.27 3 days 9 days 0.002
Parameters P value P value for time

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for groups in each group hospitalization period and blood sugar controlling re- 99

Fasting 0.204 0.009 spectively (Table 2). 100

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One hour after breakfast 0.522 0.001 In order to influence the investigation of different 101
Before lunch 0.338 0.03
therapeutic methods between two groups on the vari-

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One hour after lunch 0.523 0.118
Before dinner 0.515 0.12 ation of blood Glucose level at the particular times 103

such as fasting, pre-meal, postprandial, 12 MN, and 3

One hour after dinner 0.124 0.028
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12 AM 0.334 0.282 AM, The Repeated Measure ANOVA method has been 105
3 AM 0.301 0.08
used. Then, according to the results, the blood glucose
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level in patients at most of the measuring times (Fast- 107

74 each group) treated, inpatient. In the first group (Group ing, one hour after breakfast, before lunch and after 108
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75 A) patients were treated with regular Insulin with or dinner) in both groups were lowered remarkably dur- 109
76 without NPH, and the other group (Group B) patients ing the hospitalization period. Nevertheless, we could 110
treated with Novo-rapid Insulin with or without Lev-
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not find any meaningful differences between the two 111
78 emir Insulin. Subsequent of Insulin administration, pa- groups of study (P value 0.204) and also there are not 112
79 tients’ blood sugar checked in fasting, before and one any significant changes in the glucose level at the time
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80 hour after each meal, and also at 12 midnight, and 3 of one hour after lunch (P value 0.11), before dinner 114
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81 AM. Every time, when glucometer devices checked (P value 0.12), twelve midnight (P value 0.28), and 115
82 blood sugar, the dosage of Insulin was measured based three AM (P value 0.08) (Table 3). 116
83 on a patient’s demand. The blood glucose levels, the According to Table 4, by using the Man-Whitney
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84 period of hospitalization in the hospital, and patients test, we find out significant differences among patients 118
85 satisfaction were compared in each group by SPSS21. satisfaction from using two medicine packages. How- 119
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ever, the satisfaction rate in group B was higher than 120

group A (P value 0.038). 121

86 3. Results Average days of hospitalization along with standard 122

deviation, shortest and most prolonged period of hos- 123

87 Both groups underwent evaluation in different vari- pitalization, in each group of study are explained in 124
88 ables such as frequency of gestation, previous clinical Table 5. Non-parametric Man-Whitney test showed us 125
89 history, and age of the pregnancy, age of the mothers there are significant differences in hospitalization pe- 126
90 and their fasting blood sugar level before taking part riod between two groups. Average hospitalization days 127
91 in this study. By using Mann-Whitney and chi-square were significantly lower in group B rather than group 128
92 analyzing methods, we realized that both groups did A (P value 0.002). 129
93 not have any significant differences among mentioned
94 parameters and as a result, we could entirely relate the
95 study Results to the type of medicine which we used 4. Discussion 130

96 on patient groups (Table 1).

97 We have not seen any significant correlation be- There is no recent study which shows us to prove the 131

98 tween demographic parameters with the length of the effectiveness of two types of mentioned Insulin ther- 132
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4 F.G. Amini et al. / Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin

133 apy and also how they could be reliable in controlling Another remarkable point is the hospitalization pe- 184

134 blood sugar levels in pregnant women. Similar studies riod of patients which it was significantly (P -value 185

135 are also limited. 0.002) shorter in Novo-rapid Insulin group in compare 186

136 In this study, we tried to eliminate any bias, and we with Regular Insulin group. This crucial advantageous 187

137 paired patients in several variables such as mother’s point is not only beneficial to patient and physician in 188

138 age, previous clinical disease, age of the pregnancy, case of time-saving during the hospitalization period 189

139 frequency of pregnancy. Moreover, also, the blood but also has cost benefits to insurance and health care 190

140 sugar level of patients, when they admitted to hospital, system. 191

141 were similar between groups.

142 Consequently, we can note that the results of this
143 study based on the type of medicine and Insulin used 5. Conclusion 192

144 on patients. However, there were not any significant

145 differences between the function of Insulin which we According to this study, we can firmly suggest that 193

146 used on two study groups. using of Novo-rapid and Levemir Insulin in compare 194

147 In a study performed by Pettite and et al. in 2005, fif- with Regular and NPH Insulin is more efficient and 195

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148 teen patient’s blood glucose level was monitored, fast- could give more contentment to patients due to being 196

149 ing and after a meal, for three days in a row. In that easy to use among patients and less hospitalization pe- 197

riod advantages.

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150 study, the first day there was no Insulin, second-day pa-
tients underwent Insulin regular, and third-day Insulin In case of insurance agencies willingness to cover 199

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152 Aspart given to patients. Their study revealed that in the cost of Novo-rapid and Levemir Insulin as well 200

as the Regular Insulin we suggest the application of 201

153 two days of Insulin therapy, the blood glucose levels
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154 reduced noticeably in patients in comparison with the Novo-rapid Insulin through the health care system. 202

day whom they did not get any Insulin [11]. This re- Because of the favorable aspects of Novo-rapid In- 203
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155

156 sult also supports our data, but according to their short- sulin, the patient along with the physician and health 204

157 term study results, the effect of Insulin Aspart on pa- care system can get several benefits. However, this 205
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158 tient’s blood glucose level was better than Regular In- study and its efficacy warrant further investigations and 206

could give rise to new strategies of therapeutic inter- 207

159 sulin. However, in our study which patients followed
ventions.
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208
160 up in maximum for nine days, the results between two
161 groups of the study did not have any significant differ-
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162 ences (P value 0.20).

Acknowledgments 209
163 In another study [12], 322 women diagnosed with
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164 type 1 diabetes who, was pregnant less than ten weeks
Shahid Beheshti University of Medical Sciences fi- 210
165 or were willing to become pregnant, were treated in nancially and technically supported this study. 211
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166 two groups with Regular and Aspart Insulin. The re-
167 sults showed that Aspart Insulin caused an increase in
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168 emerging more term labor newborn in compare with Conflict of interest 212
169 Regular Insulin [12].
170 Furthermore, in a study [13] which performed on 72 The authors declare that they have no conflict of in- 213
171 GDM patients in two groups of Aspart Insulin admin- terest. 214
172 istration and diet controlling, results demonstrate that
173 in case of blood glucose controlling and hypoglycemia,
174 Aspart Insulin efficacy was better than keeping patients References 215

175 on a diet. Also, using Aspart Insulin is efficient and

176 almost safe for GDM patient [13]. [1] K.J.L.F. Gary Cunningham, S.L. Bloom, C.Y. Spong, J.S. 216

177 Besides, our study’s results showed that using Novo- Dashe, B.L. Hoffman, B.M. Casey and J.S. Sheffield, 217
in: Williams Obstetrics, New York: McGraw-Hill Educa- 218
178 rapid and Levemir Insulin can control the patient’s tion/Medical, 2014, pp. 300–301. 219
179 blood glucose level as well as Regular and NPH In- [2] A. Dornhorst, Diabetes in pregnancy, Women’s Health 220

180 sulin. One of the crucial points of this study is patient’s Medicine 2 (2005), 8–12. 221
[3] M. de Veciana et al., Postprandial versus preprandial blood 222
181 satisfaction from using Novo-rapid Insulin in compare
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182 with Regular Insulin which it could be due to using tus requiring insulin therapy, N Engl J Med 333 (1995), 1237– 224
183 Flex pen instead of syringe for injection purpose. 1241. 225
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