Gestational diabetes pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Insulin insensitivity due to hormonal changes especially during the second and third trimesters and maternal | Insulin insensitivity due to hormonal changes in pregnancy (especially during the second and third trimesters), and changes in maternal metabolism, are the main predisposing factors for acquiring gestational diabetes. | ||
==Pathophysiology== | ==Pathophysiology== | ||
Maternal metabolic changes during pregnancy varies based on the age of pregnancy, maternal nutritional status and age of mother. | Maternal metabolic changes during pregnancy varies based on the age of the pregnancy, the maternal nutritional status, and the age of the mother. | ||
===Insulin insensitivity=== | ===Insulin insensitivity=== | ||
Insulin sensitivity reduces slightly during first and second | Insulin sensitivity reduces slightly during the first and second trimester, but it decreases by 40-60% during the third trimester.<ref name="pmid8430789">{{cite journal |vauthors=Catalano PM, Tyzbir ED, Wolfe RR, Calles J, Roman NM, Amini SB, Sims EA |title=Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes |journal=Am. J. Physiol. |volume=264 |issue=1 Pt 1 |pages=E60–7 |year=1993 |pmid=8430789 |doi= |url=}}</ref><ref name="pmid2183610">{{cite journal |vauthors=Buchanan TA, Metzger BE, Freinkel N, Bergman RN |title=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 |journal=Am. J. Obstet. Gynecol. |volume=162 |issue=4 |pages=1008–14 |year=1990 |pmid=2183610 |doi= |url=}}</ref><ref name="pmid1750458">{{cite journal |vauthors=Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA |title=Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women |journal=Am. J. Obstet. Gynecol. |volume=165 |issue=6 Pt 1 |pages=1667–72 |year=1991 |pmid=1750458 |doi= |url=}}</ref> | ||
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.<ref name="pmid17596458">{{cite journal |vauthors=Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE |title=Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes |journal=Diabetes Care |volume=30 Suppl 2 |issue= |pages=S112–9 |year=2007 |pmid=17596458 |doi=10.2337/dc07-s202 |url=}}</ref> | Other changes in the 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.<ref name="pmid17596458">{{cite journal |vauthors=Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE |title=Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes |journal=Diabetes Care |volume=30 Suppl 2 |issue= |pages=S112–9 |year=2007 |pmid=17596458 |doi=10.2337/dc07-s202 |url=}}</ref> | ||
Factors affecting insulin insensitivity include: [[Estrogen|estrogens]] and [[progesterone]]<ref name="pmid7002669">{{cite journal |vauthors=Freinkel N |title=Banting Lecture 1980. Of pregnancy and progeny |journal=Diabetes |volume=29 |issue=12 |pages=1023–35 |year=1980 |pmid=7002669 |doi= |url=}}</ref>, human chorionic somatomammotropin (hCS) or [[placental lactogen]] (HPL), [[prolactin]], placental growth hormone variant (hGH-V), [[corticotropin-releasing factor]] (CRF) and [[corticotropin]], [[leptin]]<ref name="pmid9588462">{{cite journal |vauthors=Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, Hauguel-de Mouzon S |title=Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin |journal=Diabetes |volume=47 |issue=5 |pages=847–50 |year=1998 |pmid=9588462 |doi= |url=}}</ref>, [[Tumor necrosis factor-alpha|tumor necrosis factor α]] (TNF-α)<ref name="pmid12086951">{{cite journal |vauthors=Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM |title=TNF-alpha is a predictor of insulin resistance in human pregnancy |journal=Diabetes |volume=51 |issue=7 |pages=2207–13 |year=2002 |pmid=12086951 |doi= |url=}}</ref>, [[adiponectin]]<ref name="pmid15778860">{{cite journal |vauthors=Retnakaran R, Hanley AJ, Raif N, Hirning CR, Connelly PW, Sermer M, Kahn SE, Zinman B |title=Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications |journal=Diabetologia |volume=48 |issue=5 |pages=993–1001 |year=2005 |pmid=15778860 |doi=10.1007/s00125-005-1710-x |url=}}</ref>, [[resistin]], [[ghrelin]] and [[interleukin-6]]. | Factors affecting insulin insensitivity include: [[Estrogen|estrogens]] and [[progesterone]]<ref name="pmid7002669">{{cite journal |vauthors=Freinkel N |title=Banting Lecture 1980. Of pregnancy and progeny |journal=Diabetes |volume=29 |issue=12 |pages=1023–35 |year=1980 |pmid=7002669 |doi= |url=}}</ref>, human chorionic somatomammotropin (hCS) or [[placental lactogen]] (HPL), [[prolactin]], placental growth hormone variant (hGH-V), [[corticotropin-releasing factor]] (CRF) and [[corticotropin]], [[leptin]]<ref name="pmid9588462">{{cite journal |vauthors=Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, Hauguel-de Mouzon S |title=Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin |journal=Diabetes |volume=47 |issue=5 |pages=847–50 |year=1998 |pmid=9588462 |doi= |url=}}</ref>, [[Tumor necrosis factor-alpha|tumor necrosis factor α]] (TNF-α)<ref name="pmid12086951">{{cite journal |vauthors=Kirwan JP, Hauguel-De Mouzon S, Lepercq J, Challier JC, Huston-Presley L, Friedman JE, Kalhan SC, Catalano PM |title=TNF-alpha is a predictor of insulin resistance in human pregnancy |journal=Diabetes |volume=51 |issue=7 |pages=2207–13 |year=2002 |pmid=12086951 |doi= |url=}}</ref>, [[adiponectin]]<ref name="pmid15778860">{{cite journal |vauthors=Retnakaran R, Hanley AJ, Raif N, Hirning CR, Connelly PW, Sermer M, Kahn SE, Zinman B |title=Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications |journal=Diabetologia |volume=48 |issue=5 |pages=993–1001 |year=2005 |pmid=15778860 |doi=10.1007/s00125-005-1710-x |url=}}</ref>, [[resistin]], [[ghrelin]] and [[interleukin-6]]. | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]
Overview
Insulin insensitivity due to hormonal changes in pregnancy (especially during the second and third trimesters), and changes in maternal metabolism, are the main predisposing factors for acquiring gestational diabetes.
Pathophysiology
Maternal metabolic changes during pregnancy varies based on the age of the pregnancy, the maternal nutritional status, and the age of the mother.
Insulin insensitivity
Insulin sensitivity reduces slightly during the first and second trimester, but it decreases by 40-60% during the third trimester.[1][2][3] Other changes in the 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]
Factors affecting insulin insensitivity include: estrogens and progesterone[5], human chorionic somatomammotropin (hCS) or placental lactogen (HPL), prolactin, placental growth hormone variant (hGH-V), corticotropin-releasing factor (CRF) and corticotropin, leptin[6], tumor necrosis factor α (TNF-α)[7], adiponectin[8], resistin, ghrelin and interleukin-6.
Maternal metabolic changes
Basal and postprandial levels of glucose, FFAs, triglycerides, and amino acids are higher in GDM than of normal pregnancy.[9]
Maternal hyperglycemia leads to fetal hyperinsulinism, which is responsible for macrosomia and neonatal morbidity. Development of macrosomia (defined as birth weight >4000 g or above the 90th percentile for gestational age) is a frequent complication of pregnancies complicated by DM and GDM.
[10]
Increased adiposity is the primary component of the macrosomia. Infants of diabetic mothers may have up to twice the body-fat content of infants of normal mothers. [11]
Following is the schematic model of pathophysiologic aspect of disease progression and consequences.
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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ "care.diabetesjournals.org" (PDF).
- ↑ Catalano PM, Thomas A, Huston-Presley L, Amini SB (2003). "Increased fetal adiposity: a very sensitive marker of abnormal in utero development". Am. J. Obstet. Gynecol. 189 (6): 1698–704. PMID 14710101.