Gestational diabetes pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Pathophysiology
Maternal metabolic changes during pregnancy varies based on the age of pregnancy, maternal nutritional status and age of mother.
Insulin insensitivity
Insulin sensitivity reduces slightly during first and second trimesters but it decreases 40-60% during third trimester.[1][2][3] Other changes in molecular level that may lead to insulin resistant include: reduced ability of insulin to phosphorylate the insulin receptor, decreased expression of insulin receptor substrate 1 (IRS-1) and increased levels of a specific kinase.[4]
Maternal metabolic changes
Basal and postprandial levels of glucose, FFAs, triglycerides, and amino acids are higher in GDM than of normal pregnancy.[5]
Factors affecting insulin insensitivity include: estrogens and progesterone[6], human chorionic somatomammotropin (hCS) or placental lactogen (HPL), prolactin, placental growth hormone variant (hGH-V), corticotropin-releasing factor (CRF) and corticotropin, leptin[7], tumor necrosis factor α (TNF-α)[8], adiponectin[9], resistin, ghrelin and interleukin-6.[2]
Pregnancy is a state of relative insulin insensitivity. During the early part of pregnancy there is increase in insulin secretion and beta cell hyperplasia. This leads to an increase in insulin sensitivity with low fasting blood sugar levels, increased glucose uptake by peripheral tissue and glycogen storage as well as decreased hepatic gluconeogenesis. This process is crucial for the build-up of maternal adipose tissue, to be used in the later part of pregnancy. During the late phase, there is an increase in hormones such as cortisol, prolactin, progesterone and human placental lactogen which leads to a state of relative insulin resistance, possibly via a post receptor defect in the cells. This is a critical step which ensures adequate delivery of nutrients to the fetus. The pancreas respond to this increased resistance by doubling the release of insulin.
It has been found that women diagnosed with gestational diabetes already have insulin resistance at baseline with a higher level of plasma insulin levels. This state gets further aggravated by the metabolic changes associated with pregnancy. The pancreas however, is unable to cope with this additional stress of elevated level of insulin resistance. This results in an inadequate release of insulin and elevated blood sugar levels.
References
- ↑ Catalano PM, Tyzbir ED, Wolfe RR, Calles J, Roman NM, Amini SB, Sims EA (1993). "Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes". Am. J. Physiol. 264 (1 Pt 1): E60–7. PMID 8430789.
- ↑ 2.0 2.1 Buchanan TA, Metzger BE, Freinkel N, Bergman RN (1990). "Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes". Am. J. Obstet. Gynecol. 162 (4): 1008–14. PMID 2183610.
- ↑ Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA (1991). "Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women". Am. J. Obstet. Gynecol. 165 (6 Pt 1): 1667–72. PMID 1750458.
- ↑ Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE (2007). "Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes". Diabetes Care. 30 Suppl 2: S112–9. doi:10.2337/dc07-s202. PMID 17596458.
- ↑ Metzger BE, Phelps RL, Freinkel N, Navickas IA (1980). "Effects of gestational diabetes on diurnal profiles of plasma glucose, lipids, and individual amino acids". Diabetes Care. 3 (3): 402–9. PMID 7190092.
- ↑ Freinkel N (1980). "Banting Lecture 1980. Of pregnancy and progeny". Diabetes. 29 (12): 1023–35. PMID 7002669.
- ↑ Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, Hauguel-de Mouzon S (1998). "Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin". Diabetes. 47 (5): 847–50. PMID 9588462.
- ↑ Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM (2002). "TNF-alpha is a predictor of insulin resistance in human pregnancy". Diabetes. 51 (7): 2207–13. PMID 12086951.
- ↑ Retnakaran R, Hanley AJ, Raif N, Hirning CR, Connelly PW, Sermer M, Kahn SE, Zinman B (2005). "Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications". Diabetologia. 48 (5): 993–1001. doi:10.1007/s00125-005-1710-x. PMID 15778860.