What are the effects of Gestational Diabetes Mellitus on offspring?

Gestational Diabetes Mellitus:

What are the effects of Gestational Diabetes Mellitus on offspring?

Mariana Covarrubias 1935127 March 3, 2014 Evidenced Based Research DIE4564

What are the effects of Gestational Diabetes Mellitus on offspring?

Abstract
Background The increasing prevalence type 2 diabetes and obesity in children is a major burden for the individual, but also for the health economy. The purpose of this review is to examine the effects of gestational diabetes mellitus on offspring.

Research Methods The five steps for systematic review from the AND Evidence-Based Manual are used to compile this paper. The primary articles were obtained from the Florida International University online library database including AGRICOLA, MEDLINE, PubMed, Health Sciences and Nursing database, and CINAHL. Most of the participants include individuals with GDM and Type 1 Diabetes Mellitus and offspring exposed to maternal diabetes.

Results Most of the studies reviewed included retrospective cohort studies and RCTs. Almost all subjects were recruited in hospitals in Canada, India, Germany, and the U.S. Participants were recruited and given a OGTT in a hospital setting. After recruitment, follow-ups were scheduled either once or intermittently in the future. Most studies measured outcomes by performing OGTT, blood work, or questionnaires and measuring height, weight, waist circumference, BMI, and skin folds. Most studies revealed association between GDM and higher risk of becoming overweight or obese and developing T2DM, T1DM, pre-diabetes, and cardiovascular problems.

Conclusion Overall the studies provided supporting evidence to suggest that intrauterine exposure of maternal diabetes correlates with higher risks of developing diabetes, obesity, and cardiovascular risks in offspring. Identifying risk groups gives the opportunity for lifestyle or nutrition

What are the effects of Gestational Diabetes Mellitus on offspring? intervention, hopefully avoiding or reducing GDM,T2DM, obesity, and pre-diabetes in future generations.

Introduction
The increasing prevalence of obesity and type 2 diabetes in children is a major burden for the individual, but also for the economy.1 There is an increasing epidemic of obesity, metabolic syndrome, and T2DM among children and adolescents. Early detection is essential in preventing progression towards cardiovascular disease, obesity, and diabetes. 1 Identifying the risk factors of these issues is essential in providing the appropriate nutrition and lifestyle interventions to avoid or decrease the prevalence of T2DM, pre-diabetes, obesity, and cardiovascular problems.2 In order to develop preventive strategies, it is useful to identify individuals at high risk and factors that influence them . It is known that GDM influences weight development in children and several studies indicate that intrauterine exposure to diabetes increases risk for obesity and type 2 diabetes in offspring of mothers with GDM.2 In one of the first studies developed on GDM on Pima Indians, who are highly susceptible to GDM, obesity was found at all ages in offspring of mothers who had diabetes during pregnancy compared with offspring of mothers who never developed diabetes or those who developed it later in life.3 A well know predisposing factor for GDM is obesity, as the prevalence of overweight is rapidly increasing there is also an increase in GDM in the population. 4 0.3% of women are being diagnosed with T1DM at the reproductive life stage and also 36% of women are diagnosed with GDM while pregnant.5 The purpose of this research is to identify the risk factors associated with intrauterine exposure to diabetes in offspring in order to help prevent diabetes, obesity, and cardiovascular diseases from evolving through nutrition and lifestyle interventions. The research examined

What are the effects of Gestational Diabetes Mellitus on offspring? provides support on the association between GDM exposure and developing diabetes, obesity, and cardiovascular problems in the future.

Methodology
This literature review consists of eighteen primary research articles and four reviews of articles. The articles range from 2008-2013, there are no articles identified that were published more than 7 years ago. The search criteria for this review follows the guidelines on the Evidence Analysis Manual provided by the Academy of Nutrition and Dietetics. All the articles were obtained from the Florida International University Online Library Database using search engines like AGRICOLA, MEDLINE, PubMed, CINAHL, and the Health Sciences and Nursing combined database. The research collected included mostly Retrospective Cohort Studies and Randomized Control Studies. All of the studies focused on individuals with GDM or T1DM and the effects it had on offspring regarding future development of health risks.

Table 1: Search Plan, Inclusion/Exclusion Criteria

Question: Date of Literature Review: Inclusion Criteria: What are the effects of gestational diabetes on offspring? March 2014 Age: birth- 27 yrs old Setting: Hospitals in Germany, United States, India, Denmark and Canada Health Status: Any Nutrition-Related Problem or Condition: offspring of parents with GDM or T1DM Study Design Preference: 1) Cohort, 2) RCT Size of Study Groups: ranged from 20-10,000

What are the effects of Gestational Diabetes Mellitus on offspring? Study Drop-Out Rate: roughly 30-60% Year Range: 2007-2013 Language: English Exclusion Criteria:

Health Status: not offspring of parents that participated in original cohort study or not offspring exposed to GDM Nutrition Related Problem or Condition: GDM Year Range: anything before 2007

Search Terms: Search Vocabulary

Health Condition: Gestational Diabetes Mellitus Intervention: GDM, nutrition, lifestyle, OGTT, offspring, risk factors, effects, Children, pregnancy, intrauterine diabetes, insulin, prenatal exposure, diabetes, BMI

Electronic Databases

Pubmed, Medline, Agricola, and combined health sciences database from FIUs online library

Summary of Articles Number of Primary Articles Identified: 18 Identified to Review Number of Review Articles Identifies: 4 Total Number of Articles Identified: 22 Number of Articles Reviewed but Excluded: 10

Table 2: Results What are the effects of Gestational Diabetes Mellitus on offspring?
Author, Study Year, Study Purpose Study Population Intervention Outcomes Conclusion Limitations

What are the effects of Gestational Diabetes Mellitus on offspring? Design, Class Rating
Boerschmann H et al. 20102 Retrospective Cohort Study B/(+) Assess the impact of GDM on overweight risk and insulin resistance in offspring in Germany

(N)

N=232 offspring of mothers with GDM, type 1diabetes, and non-diabetes between 1989200 in Germany. Exclusion Criteria: Not offspring of women with GDM, type 1 diabetes, or non-diabetes that participate in original study between 1989-2000 in Germany.

Clausen Td et al. 20086 Retrospective Cohort Study B/(+)

Evaluate the prevalence of T2DM and prediabetes in young adult offspring of women with either diet-treated

N=597subjects (mainly Caucasian) Age: 18-27 years Exclusion Criteria: singletons only, only eldest child

232 BMI measurements of offspring of mothers with GDM were collected at ages 2, 8, and 11 and compared with those from 757 offspring of mothers with type 1 diabetes and 431 offspring of non-diabetic mothers born between 19892000. Insulin resistance was measured in 751 children at age 8 or 11, fasting blood samples were collected and resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Fasting insulin was determined using an automated immune-assay analyzer. Participants were tested with a 2-h 75-g OGTT and then separated into 4 groups according to maternal glucose metabolism:. Group 1: (168)

Over-weight prevalence increased in offspring with exposure to GDM compared to intrauterine exposure to type-1 diabetics and nondiabetics. Insulin resistance also increased in offspring exposure to GDM when compared to nondiabetics and was also associate with higher BMI.

Insulin resistance and overweight is increased in children exposed to GDM in comparison to T1DM and nondiabetic exposure. Prevalence of overweight in GDM offspring was 17.2% at age 2 years, 20.2% at age 8 years, and 31.1% at age 11 years.

Recall bias of over or underestimating growth reported by parents. Small number of subjects exposed to GDM, a larger number of subjects might change associations. Data for potential cofounders like socioeconomic status, dietary habits, and physical activity were not collected which could change some of the associations made.

Prevalence of T2DM and prediabetes in the 4 groups was 21,12,11,and 4 %. The risk of developing T2DM or

Prevalence of T2DM and prediabetes is increased among Nordic Caucasian adults. Hyperglycemic intrauterine exposure increases risk of

~50% of study participants were lost to follow-up.

What are the effects of Gestational Diabetes Mellitus on offspring?

GDM or T1DM in a Nordic Caucasian population. participated Offspring of women with diet-treated GDM, subjects diet-treated only Group 2: (141) Offspring of genetically predisposed women with a normal OGTT; subjects untreated Group 3: (160) Offspring of women with T1DM; subjects diet-treated only Group 4: (128) Offspring of women from the background population, subjects untreated Participants were diagnosed/treate d with a 3-h 100-g OGTT and National Diabetes Group criteria. Weight in offspring of participant was measured 5-7 years after to calculate sexspecific weight for-age percentiles. Women are randomly put into one of two groups: Group 1: Control Group; followed biweekly in tertiary care center with glycemic pre-diabetes was highly associate with GDM exposure. developing T2DM.

Hillier TA et al. 20077 Retrospective Cohort Study B/ (+)

Determine how ranges in maternal glucose levels during pregnancy relate to risks of childhood obesity.

N=9,439 mothers Mostly Caucasian Age: 5-7 years old Exclusion Criteria: not a participant of Kaiser Permanente Northwest or Hawaii between 19952000 with GDM performed N=89 offspring of women with GDM Age:7-11 Exclusion Criteria: If not a women who participated in

There was a positive trend for increasing childhood obesity at age 5-7 across the range of increasing maternal glucose values. (P<0.0001; 85th and 95th percentiles)

Hyperglycemia during pregnancy is highly associated with and increased risk of childhood obesity.

Follow-ups were lost due to fact that participant had to remain Kaiser Permanente members to be able to followup. GDM OGTT results are from one screening not various, which would yield more accurate results. Only 30% of original participants completed the study. Not all children who participated agreed to have an OGTT or blood work done.

Keely EJ et al. 20081 Randomized Control Trial A/ (+)

Describe the prevalence of metabolic markers of insulin resistance of GDM offspring at ages 7-11.

Of 68 children 49 had normal BMI, 8 were overweight, and 11 were obese. The children in the obese and overweight

Metabolic markers of insulin resistance in children exposed to GDM may be present in the absence of abnormal fasting or 2

What are the effects of Gestational Diabetes Mellitus on offspring?

the original RCT targets of fasting blood glucose and 1 hour postprandial blood glucose Group 2: Minimal Intervention Group; selfmonitored glucose result performed biweekly. Offspring was given a 2-hour OGTT and had blood work done, and also categorized according to height and weight on BMI scale. Group1: Offspring of diabetic mothers Group 2: Offspring of diabetic fathers Group 3:Offspring of non-diabetic parents (control subjects) Glucose, insulin, homeostasis model assessment, and skin folds were completed on all subjects. categories all had 1-3 metabolic markers while the normal BMI category had only one child with 1 metabolic marker. hour glucose values.

Krishnaveni GC et al. 20108 Retrospective Cohort Study B/(+)

Test hypothesis the GDM increases cardiovasc ular risk in Indian children.

N=514 Age: 7-9.5 years old Exclusion Criteria: Not offspring of women who completed OGTT during 1997-1998 at Holdsworth Memorial Hospital in Mysore, India.

Offspring of diabetic mother: larger skin folds, higher glucose and insulin, higher HOMA of insulin resistance and systolic blood pressure than control subjects. Offspring of diabetic fathers=larg er skin folds and higher HOMA than control subjects.

In offspring of diabetic mothers risk of diabetes, and cardiovascular increases. GDM is a strong determinant for higher adiposity and higher CVD risks.

Blood pressure was not measured. Small control group number.

Article Summaries

What are the effects of Gestational Diabetes Mellitus on offspring?

In the retrospective cohort study by Boerschmann H et al.2 mothers (GDM, T1DM, and non-diabetic) and their offspring were recruited between 1989 and 2000 Germany-wide and entered into the study before the offspring reached the age of 3 months. 232 off spring , mostly Caucasian, were able to follow-up with the study throughout the years. Offspring was followedup with visits until 14 years of age. BMI was measured at ages 2, 8, and 11 and insulin resistance was measured at age 8 or 11. Results show that prevalence of overweight and as a consequence insulin resistance id higher in offspring exposed to GDM than in offspring exposed to T1DM. This indicates that the type of maternal diabetes exposure affects overweight risk, since higher risk was associated with GDM when compared to T2DM. The retrospective cohort study by Clausen TD et al.6 aimed to evaluate the prevalence of T2DM and pre diabetes in offspring who were exposed to GDM or intrauterine T1DM. The population tested in this study was mostly Nordic Caucasian, since the study took place in Denmark. Participants were tested with a 2-h 75-g OGTT and then separated into four groups according to genetic predisposition and glucose metabolism during pregnancy. The four groups consisted of offspring of women with diet-treated GDM, offspring of genetically predisposed women with a normal OGTT, offspring of women with T1DM , and offspring of women from the background population. Offspring was then measured for height and weight and a blood glucose test was performed. Results showed significant risk increase in developing pre-diabetes and T2DM associated with intrauterine GDM or T1DM. No conflict of interest was revealed in regards to funding source as stated in the article. In the retrospective cohort study by Hillier TA et al.1 participants from the Kaiser Permanente Northwest and Hawaii between 1995-2000 were evaluated using OGTT. After 5-7 years offspring of original participants were measured for height, weight, and BMI. Results

What are the effects of Gestational Diabetes Mellitus on offspring? determined that increased hyperglycemia during pregnancy is associated with a higher risk of

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childhood obesity. The results also suggest that this risk is modifiable by treating GDM in order to decrease T2DM risk. The randomized control trial by Keely EJ et al.1 in Eastern Ontario, Ottawa, Canada where 299 women were recruited and separated into to random groups of control and minimal intervention. 89 offspring of these women were then given 2-hour OGTT and had blood work done at age 7-11. The offspring were tested for metabolic markers and categorized according to BMI, 49 children had normal BMI, 8 were overweight, and 11 were obese. The statistical analysis methods used were the Wilcoxon Mann-Whitney test to determine the relationship between insulin resistance and metabolic markers in the offspring. The HOMA was also used to calculate insulin sensitivity. Weight and height was measured and then defined on a BMI scale, offspring was classified as overweight if their BMIs were greater than the 95th percentile according to their weight and height relative to sex. The children in the obese and overweight categories all had 1-3 metabolic markers while the normal BMI category had only one child with 1 metabolic marker. The results prove that metabolic markers may be present in the absence of abnormal fasting or 2-h glucose values. In the retrospective cohort study by Krishnaveni GV et al.8 the purpose was to test the hypothesis that GDM increases cardiovascular risk factors in Indian children. The recruitment took place at Holdsworth Memorial Hospital in Mysore, India between 1997 to 1998. Out of the 630 recruited only 514 children ages 7-9.5 were separated into three groups: offspring of diabetic mothers, offspring of diabetic fathers, and offspring of non-diabetics. Glucose, insulin, homeostasis model assessment, and skin folds were completed on all subjects. The results

What are the effects of Gestational Diabetes Mellitus on offspring?

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showed significance relevance between exposure to maternal diabetes in comparison to paternal and a greater increase in cardiovascular risks.

Discussion
The five articles reviewed all show correlation between intrauterine maternal diabetes exposure and high risk in developing T2DM, pre-diabetes, obesity, and cardiovascular problems. All studies agreed that the results provided significant evidence to provide nutrition and lifestyle interventions in at risk individuals to help prevent or treat diabetes or diabetes related health risks. Knowing the risk factors associated with GDM it is easier to create lifestyle and nutrition modifications to prevent complications in the future. This research provides a stepping stone in identifying metabolic markers that suggest future complications, knowing about these issues beforehand can eliminate or prevent those risk factors from occurring. The biggest determinant of GDM is obesity and GDM is a risk factor for developing obesity in offspring. The cycle has to be broken and this research can lead the way in implementing preventative programs for those at risk instead of treating individuals who already developed T2DM or cardiovascular problems. Prevention is key at dealing with these issues and lessening the economic health burden on the economy. The studies provided gave undenying associations between GDM and high health risk factors in offspring, but the studies also had certain limitations that could have changed certain associations in the data collected. Limitations included small study population within the subgroups and also loss of followup participation due to years in between recruitment and follow-ups. The strengths of the research provided was the variation in populations and the different risk factors assessed in association with GDM. Other strengths were the categorization of the participants into groups to evaluate the difference of effects of GDM and the treatment effects on offspring.

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Table 3: Conclusion
Purpose of Evidence Appraisal Process: What are the effects of Gestational Diabetes Mellitus on offspring? Conclusion Statement: Overall the studies provided supporting evidence to suggest that intrauterine exposure of maternal diabetes is associated with higher risks of developing diabetes, obesity, and cardiovascular risks in offspring. Identifying risk groups gives the opportunity for lifestyle or nutrition intervention, hopefully avoiding or reducing GDM, T2DM, T1DM, and pre-diabetes in future generations. Conclusion Grade: I (Good/Strong), The research answers the question and gives strong evidence from strong design to support the findings in human subjects. The results are clinically important and consistent in suggesting reasons why evidence is valuable for individuals at risk. The results are free of bias and research design flaws. The sample study sizes are large enough to produce strong results.

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