Gestational Diabetes Mellitus: an Opportunity to Prevent Type 2 Diabetes and Cardiovascular Disease in Young Women

Graziano Di Cianni; Alessandra Ghio; Veronica Resi; Laura Volpe

Women's Health. 2010;6(1):97-105.

Future Perspective

Several opportunities exist for the prevention of T2DM and CVD in women with pGDM, such as education regarding risk awareness, implementation of a healthy lifestyle and pharmacological intervention.

Although GDM is a well-established risk factor for T2DM, many women could be unaware of this increased risk. Interventions are clearly needed in order to increase awareness and acceptance of the personal risk of developing T2DM in women with pGDM. Moreover, considering that not only women with GDM, but also those with mild glucose intolerance in pregnancy are at risk of CVD,^[57] public education campaigns could be performed for all women with any degree of glucose disturbance during pregnancy.

Postpartum studies of healthy diet and exercise plans should now be performed in women with pGDM in order to determine their potential benefits and to evaluate the most effective way to achieve lifestyle modification in this population. Moreover, considering that breastfeeding is associated with a reduced incidence of T2DM among both women with pGDM and women in the general population,^[58] the promotion of a combination of breastfeeding, diet and physical activity could reduce maternal T2DM risk, and might be particularly important in women with pGDM.

Several randomized clinical trials using drugs that improve insulin sensitivity have specifically studied T2DM prevention with pharmacological intervention in women with pGDM.^[54–56] Although the results of these studies are promising, it should be noted that these medications are not currently approved for use in T2DM prevention. Additional studies are still needed to evaluate the cost–effectiveness of these medications for the prevention of both T2DM and CVD, alone or in combination with new medications.

Furthermore, all women with pGDM should be offered regular checkups of their glucose tolerance, lipid profile, weight and blood pressure. In order to implement these measures, it is necessary to offer a long-term, continuous programs for these women. Based on the available evidence, a major aim during the next decade will be to implement such programs that might have an important effect on women's health.

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Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

Cite this: Gestational Diabetes Mellitus: an Opportunity to Prevent Type 2 Diabetes and Cardiovascular Disease in Young Women - Medscape - Jan 01, 2010.

Table 1. Hormones associated with modification in insulin secretion and action.
Hormone	Modification
Estrogens	↑ Insulin concentration ↑ Insulin binding
Progesterone	↓ Glucose transport ↓ Insulin binding ↓ Suppression of hepatic neoglucogenesis
Cortisol	↑ Insulin resistance ↓ Phosporylation of insulin receptor ↓ Insulin receptor substrate-1
Placental lactogen (hypothalamo–pituitary–inter-renal, growth hormone and prolactin)	↓ Insulin sensitivity ↑ Insulin secretion ↑ Insulin synthesis ↑ Utilization and glucose oxidation ↑ cAMP metabolism ↑ β-cell number ↑ β-cell mass
Glucagon	↑ Insulin resistance

Adapted from.^[7]

Table 2. Vascular function after gestational diabetes mellitus.
Study	Previous GDM (n)	Method of assessment	Results	Ref.
Hu (1988)	17	Echo tracking of aorta	Impaired	^[44]
Anastasiou et al. (1998)	33	Flow-mediated dilatation	Impaired	^[41]
Honnemann et al. (2002)	17	Flow-mediated dilatation	Normal	^[40]
Paradisi et al. (2002)	25	Flow-mediated dilatation	Impaired	^[39]
Heitritter et al. (2005)	23	Echo tracking of aorta	Stroke volume: reduced Total peripheral resistance: increased	^[33]
Bo et al. (2006)	82	Intima-media thickness	Higher	^[28]
Volpe et al. (2008)	28	Intima-media thickness	Higher	^[42]

GDM: Gestational diabetes mellitus.

Box 1. Antepartum predictors of diabetes risk after gestational diabetes mellitus.
Ethnic group Family history of maternal Type 2 diabetes BMI at diagnosis of gestational diabetes mellitus Diagnosis early in pregnancy Impaired β-cell function Magnitude of hyperglycemia Insulin therapy during pregnancy Increased body weight during pregnancy

Sidebar

Executive Summary

Gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is a common complication in pregnancy, occurring in 4–7% of pregnant women.
GDM develops as soon as β-cell secretion is no longer sufficient to compensate for physiological insulin resistance, which becomes evident in the second half of pregnancy.
Obesity and a positive family history of Type 2 diabetes (T2DM) are the most significant risk factors for the development of GDM.

GDM: a risk factor for T2DM

Although after delivery glucose tolerance returns to normal in the majority of women with GDM, for many clinicians GDM represents an early stage in the natural history of T2DM.
Factors that contribute to evolution toward overt T2DM are: an early diagnosis of GDM, fasting glucose levels before pregnancy, insulin therapy, prepregnancy obesity, positive family history of diabetes mellitus and excessive weight gain.
Cumulative incidence of T2DM increases in the first 5 years after delivery and reaches a plateau after 10 years.

GDM: a risk for cardiovascular disease

Women with previous GDM (pGDM) tend to display features of the metabolic syndrome (MS), such as hypertension, dyslipidemia and microalbuminuria, and they may present an enhanced cardiovascular risk factor profile.
MS prevalence after a GDM-complicated pregnancy is significantly higher than in women with normal pregnancy.
Impaired endothelium-dependent vasodilatation, increased vessel stiffness, early abnormalities in diastolic function and impaired cardiac autonomic function are reported in women with pGDM at a relatively young age.
The hazard ratio for cardiovascular disease (CVD) events in pGDM women is reported to be 1.71.

Prevention of T2DM & CVD

GDM must be reclassified at 6 weeks after the index pregnancy to detect persistent glucose abnormalities; women with pGDM should have an oral glucose tolerance test (OGTT) with regular intervals, beginning 1 year after pregnancy. Markers of the MS, blood pressure and lipid profile may be investigated in addition to the OGTT.
To reduce the risk of progressing to diabetes and other metabolic abnormalities, lifestyle changes with increased physical activity, weight loss and a healthy diet must be recommended to these women.
Several randomized clinical trials, using drugs that ameliorate insulin action, have specifically studied diabetes prevention with a pharmacologic intervention in women with pGDM.

Future perspective

Interventions are needed in order to increase awareness and acceptance of the personal risk for the development of T2DM in women with pGDM. Public education campaigns could help to increase patient risk-awareness.
Additional pharmacological studies are still needed to evaluate the cost–effectiveness of the prevention of both T2DM and CVD.
Long-term, continuous programs specifically addressed to women with pGDM could be performed in order to permit them to regularly check glucose tolerance, lipid profile, blood pressure and other parameters aimed at improving women's health.

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