Insulin Resistance and Miscarriage

39% of women with repeat miscarriage fail OGTT; Metformin lowers miscarriage rate

Twenty-nine (39.15%) of the patients in the group with recurrent miscarriage were found to have an abnormal glucose tolerance test result compared with just four (5.4%) patients in the normal pregnancy group. The miscarriage rate was significantly reduced after metformin therapy in patients without PCOS in comparison to the placebo group (15% vs. 55%). CONCLUSION(S): This study indicates an important link between an abnormal glucose tolerance test and a history of recurrent miscarriage. It was also found that metformin therapy improves the chances of a successful pregnancy in patients with an abnormal glucose tolerance test.
http://www.ncbi.nlm.nih.gov/pubmed/18001723

27% of women with repeat miscarriage have high fasting insulin, despite normal glucose levels

Among the women with recurrent miscarriage, 27% demonstrated insulin resistance, whereas only 9.5% of the matched controls were insulin resistant (odds ratio 3.55). The recurrent miscarriage and control groups were similar with respect to age, ethnicity, and BMI. The recurrent miscarriage and control groups had similar fasting glucose levels and glucose-to-insulin ratios. However, fasting insulin levels > or =20 microU/mL were statistically different between the two groups (odds ratio 3.92).
http://www.ncbi.nlm.nih.gov/pubmed/12215322

High HbA1c associated with miscarriage

Pregnant women with poor glycemic control had higher incidence of miscarriage. CONCLUSIONS: We could not support the hypothesis of reduced antioxidant protection (low selenium and glutathione-peroxidase levels) as a causative factor in the pathogenesis of miscarriage in diabetic patients. Our study results showed that poor metabolic control of diabetes (high Hb A1-c) in the first trimester of pregnancy had a primary role in the occurrence of early miscarriages. We could speculate that the early hyperglycemic maternal-fetal environment most probably plays a role of an additional stress to the developing embryo.
http://www.ncbi.nlm.nih.gov/pubmed/17168489

Blood glucose is higher in recurrent miscarriage

The plasma levels of glucose were significantly higher in habitual miscarriage than in controls.
http://www.ncbi.nlm.nih.gov/pubmed/9857484

Fasting insulin >20, but not fasting glucose associated with higher miscarriage risk

The observed differences between age, fasting glucose and fasting glucose to fasting insulin ratio levels in case and control groups were not significant but it was significant about fasting insulin. Fasting insulin of < 20 μu/ml or ≥ 20 μu/ml in case and control group was significant. CONCLUSION: Current study showed that in women with repeat miscarriage, in Iranian race like Americans, frequency of insulin resistance in high, therefore there is a probability of the degree of insulin resistance in women with repeat miscarriage.

http://www.ncbi.nlm.nih.gov/pubmed/22405326


Improving insulin resistance lowers risk of miscarriage in PCOS subjects

Continuous use of an insulin sensitizer in PCOS patients during pregnancy significantly reduced incidence of miscarriage and intrauterine growth restriction.
http://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2008.00856.x/full

High HOMA-IR, but not obesity or PCOS, associated with miscarriage risk

This is a cohort study of 107 patients who achieved their first pregnancy after infertility treatment in a tertiary medical center. A homeostasis model assessment of insulin resistance (HOMA-IR) was carried out. The association of insulin resistance with the risk of miscarriage was significant after adjusting for other risk factors. The effect of overweight/obesity and polycystic ovarian syndrome was not statistically significant in the multivariate model.
http://www.ncbi.nlm.nih.gov/pubmed/17244790

No association found between fasting glucose or insulin and recurrent miscarriage in small study

There was no significant difference in the mean fasting glucose for the study and control patients (5.5 vs. 5.3 mmol/dl) (99 vs. 95.4 mg/dl) and in the mean fasting insulin (15.0 and 12.9 mU/l). There was no significant difference in the insulin resistance of both groups as calculated using the Homeostasis Model Assessment and the fasting glucose insulin ratio of <4.5. Conclusion: Insulin resistance was not significantly associated with recurrent miscarriage in our study. (Small study group of only 65 women.)
http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=000098363

High blood sugar leads to delayed fetal growth in the first trimester

Forty insulin-dependent diabetic women in the first trimester of pregnancy were studied. Fetal crown-rump length was measured by ultrasound and related to maternal hemoglobin A1c. Thirty mothers with normal size fetuses had an average hemoglobin A1c level of 7.8%. Ten mothers had fetuses that were smaller than normal (equivalent to eight to 14 days less growth) and also had higher hemoglobin A1c, 8.9%, indicating a more poorly controlled diabetes. Careful metabolic compensation in very early diabetic pregnancy should therefore be attempted to prevent induction of early fetal growth delay.
http://www.ncbi.nlm.nih.gov/pubmed/6462566

Insulin negatively affects fetal growth

60 women with singleton pregnancy, between 12th and 14th weeks, were included to the study. The percentiles of fetal crown-rump length were negatively associated with the adiponectin and insulin plasma concentrations. Also there were correlation between fetus crown-rump length percentile and the insulin sensitivity and the ratio of adiponectin to leptin concentration. Conclusions: The results of this study imply that adiponectin and insulin maternal plasma concentration may have a role in early determination of fetal growth.
http://www.kenes.com/dip09/cd/pdf/404.pdf


Women with recurrent miscarriage more likely to have insulin resistance in early pregnancy

Pregnant women with a history of recurrent miscarriage were included in the patient group, while those with no history of abnormal pregnancy were included in the control group. Both groups consented to undertake an oral glucose tolerance test and insulin-releasing test between the 5th and 13th weeks of pregnancy. RESULTS: The area under the curve of glucose and area under the curve of insulin were higher in the patient group than in the control group. The composite insulin sensitivity index of the patient group was lower than that of the control group. The differences in these three parameters between the groups were statistically significant. CONCLUSION: Women with a history of recurrent miscarriage are at an increased risk for insulin resistance during the first trimester of a new pregnancy.

http://www.ncbi.nlm.nih.gov/pubmed/21952420

Women with recurrent miscarriage have higher fasting blood glucose and insulin

No significant differences in age and BMI index were found between the recurrent miscarriage and control subjects. The mean number of abortions was 3.04 in the study and 0.2 in the control group. The mean fasting glucose value was 100.84 in the study group, and 89.67 in the control group. Also, the mean fasting insulin value was 15.51 in the study group and 7.17 in the control group. The mean glucose/ insulin ratio was 12.24 in the study group and 28.27 in the control group, and the mean HOMA-IR value was 4.16 in the study group and 1.62 in the control group. CONCLUSION:Compared with the control group, patients with repeat miscarriage were more likely to have insulin resistance.

http://www.ncbi.nlm.nih.gov/pubmed/21952420


Diabetic women are likely to have mild early fetal growth delay


At 12 wk, the mean fetal crown-rump length was 58.5 mm for diabetic subjects and 60.6 mm for nondiabetic subjects. Early fetal growth delay did not predict a reduced birth weight at term. Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present
http://www.ncbi.nlm.nih.gov/pubmed/1516479


Gestational diabetes associated with early growth delay in pregnancy

Ultrasound scanning has revealed that some fetuses of women with insulin-dependent diabetes are smaller than normal in early pregnancy as judged by the crown-rump length. This early growth delay is negatively correlated to the quality of diabetes regulation. Women with gestational diabetes had fetuses that were on average 4.5 days smaller than expected from the menstrual history. Apparently, the expectedly modest metabolic disturbances in early pregnancy of women with gestational diabetes are able to interfere with normal embryonic growth.
http://www.ncbi.nlm.nih.gov/pubmed/3996768

Poorly controlled diabetes leads to fetal growth delay in early pregnancy

Mothers with normal size fetuses had an average hemoglobin A1c level of 7.8%. Mothers with fetuses that were smaller than normal (equivalent to eight to 14 days less growth) had higher hemoglobin A1c, 8.9%, indicating a more poorly controlled diabetes. Careful metabolic compensation in very early diabetic pregnancy should therefore be attempted to prevent induction of early fetal growth delay.
http://www.ncbi.nlm.nih.gov/pubmed/6462566


Inhibin A (which is low in women who miscarry) is lower in diabetic women.
http://www.ncbi.nlm.nih.gov/pubmed/19004405