Affecting approximately 7% of all pregnancies, gestational diabetes mellitus (GDM) can not only adversely affect the foetus, but also increase the mother’s risk of developing type 2 diabetes. This article reviews the pathogenesis of GDM and insulin resistance and the links to diabetes following the pregnancy, as well as discussing clinical practice recommendations.
by Dr Jane Kapustin

Gestational diabetes mellitus (GDM), defined as impaired glucose tolerance first diagnosed during pregnancy, affects approximately 7% of all pregnancies or greater than 200,000 women annually in the United States alone. Foetal complications such as macrosomnia, neonatal hypoglycaemia, congenital anomalies and prenatal mortality are associated with GDM, but maternal risks for developing type 2 diabetes are also associated with the condition [1,2]. Insulin resistance later has been positively linked with insulin resistance during pregnancy [3], and women who experience GDM present an opportunity to conduct early detection and develop interventions to prevent type 2 diabetes from occurring. The incidence of GDM in the US has increased dramatically over the last 20 years from 2.9% (the average reported in the 1980s) to estimates ranging from 8.8-12% [4,5] presumably due to the rise in the number of overweight and obese pregnant women [6,7]. 

Because type 2 diabetes can be prevented or at least delayed with appropriate lifestyle changes [3,8], this vulnerable group represents a logical target for preventive efforts. However, there are many problems with such preventive healthcare for this group, including a lack of awareness of the need for lifestyle changes, poor primary care efforts to detect and intervene, and poor healthcare provider adherence to practice recommendations. This article reviews the pathogenesis of GDM and insulin resistance, risk factors, links to diabetes following the pregnancy, clinical practice recommendations for women who experienced GDM, and problems associated with adherence to practice guidelines. Evidence-based management and preventive strategies will be included along with several economic and policy implications.
 
Pathogenesis of GDM
In GDM, the otherwise essentially normal pregnancy is marked by progressive insulin resistance beginning at mid-term and continuing throughout the third trimester. Maternal adiposity, combined with hormones produced by the placenta, account for the development of insulin resistance characteristic of GDM [9].

The definition of GDM applies regardless of whether insulin is necessary for treatment, or if glucose intolerance persists after the pregnancy. The American Diabetes Association (ADA) recommends that the patient be reclassified at the six week, postpartum visit via another two hour oral glucose tolerance test OGTT [11]. The majority of patients with GDM will be adequately managed with medical nutrition therapy and exercise, but for those who cannot maintain a fasting glucose below 95mg/dL, pharmacological management with insulin is recommended [12]. 

Insulin resistance and impaired glucose tolerance (persistently elevated glucose levels that are too high, but not diagnostic for diabetes) may persist following the pregnancy and are maternal complications that are often accompanied by other long-term disease risks such as cardiovascular disease, hyperlipidaemia, impaired endothelial function and hypertension [4,13,14].

Early in the pregnancy, increased oestrogen, progesterone, prolactin and other pregnancy- related hormones (cortisol, growth hormone) lead to an insulin resistant state. Lower glucose levels, promotion of fat deposition and increased appetite often ensue. Insulin sensitivity declines steadily as the pregnancy progresses [2,15] in an effort to ensure adequate foetal glucose supply during a normal pregnancy. The insulin resistance during this phase of pregnancy approaches the level seen with patients with type 2 diabetes, and this degree of insulin resistance rapidly abates following the delivery [3]. 

Beta cell function during a normal pregnancy will increase insulin secretion, thereby maintaining normal glucose levels. However, a woman with GDM does not demonstrate an adequate secretion of insulin during this state of insulin resistance, and hyperglycaemia will ensue. First phase loss of insulin release is a typical marker for beta cell loss seen with GDM [2,3].

Although insulin resistance and resultant type 2 diabetes has demonstrated some genetic linkage, no single gene can be implicated in the development of diabetes. Environmental factors such as obesity and inactivity influence the chances of developing diabetes, and many people may lower their risk for type 2 diabetes by losing weight and being more active [5,16].  Small studies have demonstrated that genes affecting the sensitisation  of glucose by beta cells, which may regulate body composition, may be implicated in GDM. Women with GDM demonstrate differences in these genetic factors compared to control women who do not develop GDM during their pregnancies [3]. In approximately 5% of women with GDM, there is a defect in the beta cell that explains the insulin resistance; this is most often a mutation in the glucokinase gene on chromosome 7 [2].

The conversion of GDM to type 2 diabetes following the index pregnancy is particularly high for the first five years after the delivery [6]. Overweight women who continue to demonstrate impaired glucose intolerance, or persistently elevated glucose levels just under the ADA diagnostic criteria of 126 mg/dL, have an exceedingly high risk of developing type 2 diabetes. The risk is estimated at 2.6%-70% in 5-10 years at a rate of about 16% per year [1]. That risk is estimated at 11-70% depending on particular risk factors, ethnic backgrounds, the heterogeneity of diagnostic tests used to identify the women with abnormal glucose levels, the length of investigator follow-up and participant retention factors associated with any particular study [17].

Given that approximately 8.8 to 12% of all pregnancies involve some level of glucose dysfunction and that the incidence of such cases is increasing, the probability of developing type 2 diabetes is likely to continue to climb. Women who continue to experience persistent impaired glucose intolerance are a critical group to identify and target for primary prevention efforts [6].

Clinical practice recommendations
Adherence to medical guidelines developed for disease states such as GDM needs to be assessed and monitored. The ADA and the American College of Gynecology and Obstetrics (ACOG) have developed and published their practice recommendations regarding the routine postpartum care given to women who develop GDM during pregnancy [11], [18].

The ADA recommends that women with GDM be re-classified at six weeks after the index pregnancy to detect persistent glucose abnormalities [11]. For those who maintain impaired fasting glucose or glucose intolerance after the pregnancy, annual glucose testing should be implemented. Intensive medical nutritional teaching and regular exercise should be instituted. All patients should be educated regarding lifestyle modifications that can reduce the risk of insulin resistance, including weight reduction, exercise and diet modification. Patients should be advised to seek medical attention if they develop signs and symptoms of hyperglycaemia. Finally, the offspring of women with GDM should be followed closely for the development of obesity and/or abnormalities of glucose tolerance [11]. ACOG [18] has established similar guidelines of care that include close monitoring of women following GDM. Referrals to a diabetes educator, nutritionist, and/or primary care practitioner are encouraged in addition to other similar recommendations.

Follow-up recommendations for women who experienced GDM are well defined; however, routine follow-up is often not maintained, due in part to a lack of primary care surveillance in a relatively young, mobile population, loss of follow-up after the delivery, mothers’ underestimations of their risks of type 2 diabetes, and difficulties associated with adherence to diet and exercise in women busy providing care for young children [1]. Other factors implicated in low adherence rates for follow-up include patient denial, fear of needle punctures associated with labwork and busy family life. 

Mokdad et al. [5] demonstrated that primary care providers did not consistently provide patients with advice about diet, weight loss and exercise even if they were obese and sedentary. Thus, opportunities for prevention of future disease are often missed. Research has shown that clinicians are more likely to follow guidelines when certain features are in place to facilitate their use, including standing orders, reminder systems, audit tools, clinician in-service education, re-designed office forms, order forms and other pre-printed material, electronic medical records and computerised reminder systems [19-23].

Policy implications
A conversion rate to type 2 diabetes of 50% in this group of patients will add substantially to the costs of diabetes care in the US, an estimated addition of approximately $331 million dollars per year [6]. Considering the high costs associated with diabetes, the associated risks of developing type 2 diabetes following an index pregnancy makes GDM an important precursor that healthcare providers should strive to detect and manage.
 
Tuomilehto et al [24] estimate that comprehensive healthcare for women of childbearing-age prevents up to 58% of susceptible women from developing type 2 diabetes over a three to four year period of time. A study conducted in 1993 demonstrates that reducing the maternal conversion of GDM to type 2 diabetes by 50% would save the US approximately $330 million over ten years [25].
The policy implications for offering comprehensive preventive care that includes diet, weight management and exercise advice for this vulnerable population are significant. Economically, preventing or at least delaying the progression of diabetes may benefit private as well as public insurers. Considering that about 25% of healthcare spending is now attributed to treatment of obesity complications such as diabetes, it is important to explore ways to reduce if not prevent obesity and ensuing diabetes in segments of the population [26]. 

With 60% of the United States population deemed overweight or obese, implementing prevention programmes should be a high priority for public health initiatives. For major US insurers including Medicare and Medicaid, the costs saved by preventing or at least delaying the progression of diabetes are significant. Additionally, the quality of life for these potential diabetics can be maintained if disease is avoided completely, and life threatening diseases such as cardiovascular events (stroke and heart attack), kidney disease, eye disorders and infections can be avoided [27]. Therefore, offering comprehensive preventive care that includes diet, weight management and exercise advice for this vulnerable population would be appropriate, potentially life saving and cost-effective.

Conclusions
In summary, GDM is a serious sign of impending diabetes for many high-risk women. Despite this many patients are unaware of their risk, and preventive opportunities are missed. Extensive literature documents deficiencies in the  attention of healthcare practitioners to preventive approaches [28-30]. The implications of prevention are profound in terms of cost-savings for the individual and the healthcare system if significant numbers of these high-risk women can avoid or at least postpone diabetes development until much later in life. Preventing diabetes in these patients removes the necessity of adhering to a more restrictive diet, avoids the need for expensive medications with associated toxicities, and  daily or more frequent glucose monitoring via finger stick method. Most importantly the long-term, and often life-threatening, complications of diabetes such as nephropathy, retinopathy, neuropathy and heart disease are avoided. There appears to be an opportunity to offer lifestyle modification advice to this population to help reduce the problem of obesity during pregnancy. 

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A detailed list of references is available from the author.

The author
Jane Kapustin, PhD, CRNP, BC-ADM
Associate Professor and
Assistant Dean for Master’s Studies,
University of Maryland School of Nursing
Nurse Practitioner,
Joslin Diabetes Center,
Baltimore,
MD 21201
USA

President of IDF calls for government focus and spending on diabetes and other NCDs

The International Diabetes Federation (IDF) announced that its President, Professor Martin Silink, has called on governments worldwide to recognise the severe impact of diabetes and other non-communicable diseases and take immediate action to ameliorate the threat.
Speaking at the United Nations Economics and Social Council (ECOSOC) annual ministerial review and regional ministerial meeting on NonCommunicable Diseases in Doha, Qatar on May 10-11, Professor Silink urged governments, the United Nations and the World Health Organisation to recognise the impact of non-communicable diseases including diabetes on global health, and to include them in the United Nations Millennium Development Goals (MDGs) and development aid programmes.
President Silink stated that non-communicable diseases such as diabetes, cardiovascular diseases, cancers and chronic respiratory diseases account for 60% of all deaths worldwide, with the majority of these deaths occurring in low-and middle-income countries. Non-communicable diseases are a major and growing economic burden to individuals and their families and impose a heavy toll on healthcare systems and society. Despite the growing disease burden of non-communicable diseases, they have not been included in the MDGs.
Silink said that the global epidemic of diabetes and other non-communicable diseases was hitting the poorest hardest. Four in five deaths from NCDs now occur in low and middle-income countries. The low-cost solutions to prevent many of these deaths were yet to be implemented. Without decisive action, the NCD burden threatened to undermine the benefits of improving standards of living, education and economic growth in many countries.
He added that the global diabetes community was waiting for UN Member States to follow through on the promise of the UN Resolution on diabetes.
www.idf.org