Diabetic retinopathy in pregnancy1. R M BEST, 2. U CHAKRAVARTHY

+ Author Affiliations 1. Department of Ophthalmology, Queens University of Belfast 2. Royal Victoria Hospital, Belfast BT12 6BA Diabetic retinopathy is one of the major causes of preventable blindness in the UK and USA in those aged between 24 and 64 years.1 For a proportion of diabetic women, the first half of this period coincides with peak fertility and childbearing years. Diabetic eye disease may develop for the first time during pregnancy, and visual loss at this stage has serious implications for both the patient and her family. In the past, the prognosis for pregnancy in diabetic women with microvascular disease was so poor that many physicians advised avoidance or termination of pregnancy.2With the recognition that the level of glycaemia during pregnancy is directly related to the incidence of congenital malformations, the emphasis on the management of diabetic pregnancy has been one of meticulous control of blood sugar and this has undoubtedly resulted in lower rates of fetal malformations. However, intensive control of glycaemia may carry risks to diabetic mothers particularly to those with established microvascular diseases such as retinopathy and nephropathy. Studies on the influence of pregnancy on the natural history of diabetic retinopathy have shown that deterioration is frequently observed.3 4 Until recently there has been controversy as to whether the progression of retinopathy which occurs in such women is due to the natural tendency of diabetic retinopathy to worsen or to unique factors operative during pregnancy. Several major studies have gone some way towards explaining the mechanisms underlying progression of retinopathy during pregnancy. Klein et al performed a prospective study on a large series of individuals, comprising 171 pregnant and 298 non-pregnant insulin dependent diabetic women.5 The level of diabetic retinopathy in the first trimester was assessed using standard retinal photographs and compared with postpartum photographs. After adjusting for duration of diabetes, glycaemic control, and blood pressure current pregnancy was [Full text of this article] http://bjo.bmj.com/content/81/3/249.extract6. Dibble CM, Kochenour NK, Worley RJ, Tyler FH, Schwartz M. Effect of pregnancy on diabetic retinopathy. Obstet Gynaecol. 59: 699-704; 1982 7. Soubrane G, Canivet J, Coscas G. Influence of pregnancy on the evolution of background retinopathy. Int Ophthalmol Clin. 8: 249-255; 1985 8. The Diabetes Control and Complications Trial Research Group. Effect of pregnancy on microvascular complications in the Diabetes Control and Complications Trial. Diabetes Care 23: 1084-1091; 2000 9. Axer-Siegel R, Hod M, Fink-Cohen S, Kramer M, Weinberger D, Schindel B, Yassur Y. Diabetic retinopathy during pregnancy.

Ophthalmology 103(11): 1815-1819; 1996 10. MMWR. Blindness caused by diabetes-Massachusetts, 19871994. MMWR-Morbidity & Mortality Weekly Report 45: 937941; 1996 11. Trautner C, Icks A, Haastert B et al. Incidence of blindness in relation to diabetes. A population-based study. Diabetes Care 20: 1147-1153; 1997 12. Dinn RB, Harris A, Marcus PS. Ocular changes in pregnancy. Obstet Gynecol Surv. Feb 58(2):137-44; 2003 13. Klein R, Klein BEK, Magli YL, Brothers RJ, Meuer SM, Moss SE, David MD. An alternative method of grading diabetic retinopathy. Ophthalmology 93: 1183-1187; 1986 14. Lapolla A, Cardone C, Negrin P, Midena E, Marini S, Gardellin C, Bruttomesso D, Fedele D. Pregnancy does not induce or worsen retinal and peripheral nerve dysfunction in insulindependent diabetic women. J Diabetes Complications 12: 74-80; 1998 15. Lovestam-Adrian M, Agardh CD, Aberg A, Agardh E. Preeclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in type I diabetic patients. Diabet Med. 14: 1059-1065; 1997 16. Chen HC, Newsom RS, Patel V, Cassar J, Mather H, Kohner EM. Retinal blood flow changes during pregnancy in women with diabetes. Invest Ophthalmol Vis Sci. 35(8): 3199-3208; 1994 17. Loukovaara S, Harju M, Kaaja R, Immonen I. Retinal capillary blood flow in diabetic and nondiabetic women during pregnancy and postpartum period. Invest Ophthalmol Vis Sci. 44(4):14861491; 2003 18. Schocket LS, Grunwald JE, Tsang AF, DuPont J. The effect of pregnancy on retinal hemodynamics in diabetic versus nondiabetic mothers. Am J Ophthalmol. 128(4): 477-484; 1999 19. Klein BE, Moss SE, Klein R. Effect of pregnancy on progression of diabetic retinopathy. Diabetes Care 13(1): 34-40; 1990 20. Lauszus F, Klebe JG, Bek T. Diabetic retinopathy in pregnancy during tight metabolic control. Acta Obstet Gynecol Scand. 79(5): 367-370; 2000 21. Chew EY, Mills JL, Metzger BE, Remaley NA, JovanovicPeterson L, Knopp RH, Conley M, Rand L, Simpson JL, Holmes LB et al. Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Diabetes Care 18(5): 631-637; 1995 22. Shamoon H, Duffy H, Fleischer N, Engel S, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 329(14): 977; 1993 23. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 341(8856): 1306-1309; 1993 24. McCulloch DK. Pathogenesis and natural history of diabetic retinopathy. Up-To-Date Online V11.3. 2002

148 McGill Journal of Medicine 200525. Sharp PS, Fallon TJ, Brazier OJ, Sandler L, Joplin GF, Kohner EM. Long-term follow-up of patients who underwent yttrium-90 pituitary implantation for treatment of proliferative diabetic retinopathy. Diabetologia 30(4): 199-207; 1987 26. Rosenn B, Miodovnik M, Kranias G, Khoury J, Combs CA, Mimouni F, Siddiqi TA, Lipman MJ. Progression of diabetic retinopathy in pregnancy: association with hypertension in pregnancy. Am J Obstet Gynaecol. 166(4): 1214-1218; 1992 27. Sheth BP. Does pregnancy accelerate the rate of progression of diabetic retinopathy? Current Diabetes Reports 2(4): 327-330; 2002 28. Diabetic Retinopathy. Preferred Practice Patterns (pamphlet).

San Francisco, CA: The American Academy of Ophthalmology 13: 28; 1998 29. Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL 3rd, Klein R. Diabetic retinopathy. American Diabetes Association: Position Statement. Diabetes Care 23: S73-S76; 2000 30. Anonymous. Effect of pregnancy on microvascular complications in the Diabetes Control and Complications Trial. Diabetes Care 23: 1084-1091; 2000

Jeff Van Impe, MD, will be attending McMaster University for his first year of residency in Psychiatry. His research interests have shifted from Ophthalmology to substance abuse and addiction.

Effect of Pregnancy on Diabetic Nephropathy and RetinopathyJ Coll Physicians Surg Pak Feb 2004;14(2):75-8.Bahawal Victoria Hospital, Bahawalpur

Objective: To determine whether pregnancy worsens renal function in women with diabetic nephropathy and the effect of pregnancy on diabetic retinopathy. Design: Cross-sectional analytical study. Place and Duration of Study: The study was conducted in OPD, Bahawal Victoria Hospital, Bahawalpur from September 1997 to June 2003. Subjects and Methods: Thirty-five patients (aged 20-36 years ) identified with diabetic nephropathy and moderate to severe renal dysfunction(creatinine {Cr} > 1.4 mg/dl) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate (GFR) were estimated. An equal number of non-pregnant premenopausal type I diabetic women with similar degrees of renal dysfunction served as controls for non-pregnant rate of decline of renal function and potential contributing factors. Student`s t-test and repeated measures analysis of variance were analyzed. Results: Mean serum Cr rose from 1.8 mg/dl prepregnancy to 2.5 mg/dl in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%.Exacerbation of hypertension or pre-eclampsia occurred in 73% and 71% of these showed acceleration of disease during the pregnancy. All the patients had diabetic retinopathy, though proliferative retinopathy was diagnosed and treated in only 54.5.% prepregnancy. The retinopathy progressed, requiring laser therapy, in 45.4%. Macular edema was noted in 6 of the patients. Other diabetic complications included peripheral and autonomic neuropathy in 8 patients. Conclusion: Pregnancy induced progression is seen in the decline of renal functions. Patients with diabetic nephropathy were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy. Forty-five percent of the patients had permanent decline in GFR in association with pregnancy. Category: Obstetrics and Gynecology Keywords: Diabetes Mellitus. Pregnancy. Diabetic Complications. Diabetic Nephropathy. Diabetic Retinopathy. Nephropathy. Retinopathy. Click here for Full Text Article

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DIABETIC RETINOPATHYWhat is diabetic retinopathy? Diabetic retinopathy is a complication of diabetes and a leading cause of blindness. It occurs when diabetes damages the tiny blood vessels inside the retina, the light-sensitive tissue at the back of the eye. A healthy retina is necessary for good vision. If you have diabetic retinopathy, at first you may notice no changes to your vision. But over time, diabetic retinopathy can get worse and cause vision loss. Diabetic retinopathy usually affects both eyes.What are the stages of diabetic retinopathy?

Diabetic retinopathy has four stages:1. Mild Nonproliferative Retinopathy. At this earliest stage, microaneurysms occur. They are small areas of balloon-like swelling in the retina's tiny blood vessels.

2. Moderate Nonproliferative Retinopathy. As the disease progresses, some blood vessels that nourish the retina are blocked.

3. Severe Nonproliferative Retinopathy. Many more blood vessels are blocked, depriving several areas of the retina with their blood supply. These areas of the retina send signals to the body to grow new blood vessels for nourishment.

4. Proliferative Retinopathy. At this advanced stage, the signals sent by the retina for nourishment trigger the growth of new blood vessels. This condition is called proliferative retinopathy. These new blood vessels are abnormal and fragile. They grow along the retina and along the surface of the clear, vitreous gel that fills the inside of the eye.

By themselves, these blood vessels do not cause symptoms or vision loss. However, they have thin, fragile walls. If they leak blood, severe vision loss and even blindness can result.Who is at risk for diabetic retinopathy?

All people with diabetes--both type 1 and type 2--are at risk. That's why everyone with diabetes should get a comprehensive dilated eye exam at least once a year. Between 40 to 45 percent of Americans diagnosed with diabetes have some stage of diabetic retinopathy. If you have diabetic retinopathy, your doctor can recommend treatment to help prevent its progression. During pregnancy, diabetic retinopathy may be a problem for women with diabetes. To protect vision, every pregnant woman with diabetes should have a comprehensive dilated eye exam as soon as possible. Your doctor may recommend additional exams during your pregnancy.How does diabetic retinopathy cause vision loss?

Blood vessels damaged from diabetic retinopathy can cause vision loss in two ways:1. Fragile, abnormal blood vessels can develop and leak blood into the center of the eye, blurring vision. This is proliferative retinopathy and is the fourth and most advanced stage of the disease.

2. Fluid can leak into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, blurring vision. This condition is called macular oedema. It can occur at any stage of diabetic retinopathy, although it is more likely to occur as the disease progresses. About half of the people with proliferative retinopathy also have macular oedema Does diabetic retinopathy have any symptoms?

Diabetic retinopathy often has no early warning signs. Don't wait for symptoms. Be sure to have a comprehensive dilated eye exam at least once a year.What are the symptoms of proliferative retinopathy if bleeding occurs?

At first, you will see a few specks of blood, or spots, "floating" in your vision. If spots occur, see your eye care professional as soon as possible. You may need treatment before more serious bleeding occurs. Haemorrhages tend to happen more than once, often during sleep. Sometimes, without treatment, the spots clear, and you will see better. However, bleeding can reoccur and cause severely blurred vision. You need to be examined by your eye care professional at the first sign of blurred vision, before more bleeding occurs. If left untreated, proliferative retinopathy can cause severe vision loss and even blindness. Also, the earlier you receive treatment, the more likely treatment will be effective.How are macular oedema and diabetic retinopathy detected?

Macular oedema and diabetic retinopathy are detected during a comprehensive eye exam that includes:

Visual acuity test. This eye chart test measures how well you see at various distances.

Dilated eye exam. Drops are placed in your eyes to widen, or dilate, the pupils. Your eye care professional uses a special magnifying lens to examine your retina and optic nerve for signs of damage and other eye problems. After the exam, your close-up vision may remain blurred for several hours.

Tonometry. An instrument measures the pressure inside the eye. Numbing drops may be applied to your eye for this test.

Your eye care professional checks your retina for early signs of the disease, including:

Leaking blood vessels.

Retinal swelling (macular oedema).

Pale, fatty deposits on the retina--signs of leaking blood vessels.

Damaged nerve tissue.

Any changes to the blood vessels.

If your eye care professional believes you need treatment for macular oedema, he or she may suggest a fluorescein angiogram. In this test, a special dye is injected into your arm. Pictures are taken as the dye passes through the blood vessels in your retina. The test allows your eye care professional to identify any leaking blood vessels and recommend treatment.How is a macular oedema treated?

Macular oedema is treated with laser surgery. This procedure is called focal laser treatment. Your doctor places up to several hundred small laser burns in the areas of retinal leakage surrounding the

macula. These burns slow the leakage of fluid and reduce the amount of fluid in the retina. The surgery is usually completed in one session. Further treatment may be needed. A patient may need focal laser surgery more than once to control the leaking fluid. If you have macular oedema in both eyes and require laser surgery, generally only one eye will be treated at a time, usually several weeks apart. Focal laser treatment stabilizes vision. In fact, focal laser treatment reduces the risk of vision loss by 50 percent. In a small number of cases, if vision is lost, it can be improved. Contact your eye care professional if you have vision loss.How is diabetic retinopathy treated?

During the first three stages of diabetic retinopathy, no treatment is needed, unless you have macular oedema. To prevent progression of diabetic retinopathy, people with diabetes should control their levels of blood sugar, blood pressure, and blood cholesterol. Proliferative retinopathy is treated with laser surgery. This procedure is called scatter laser treatment. Scatter laser treatment helps to shrink the abnormal blood vessels. Your doctor places 1,000 to 2,000 laser burns in the areas of the retina away from the macula, causing the abnormal blood vessels to shrink. Because a high number of laser burns are necessary, two or more sessions usually are required to complete treatment. Although you may notice some loss of your side vision, scatter laser treatment can save the rest of your sight. Scatter laser treatment may slightly reduce your colour vision and night vision. Scatter laser treatment works better before the fragile, new blood vessels have started to bleed. That is why it is important to have regular, comprehensive dilated eye exams. Even if bleeding has started, scatter laser treatment may still be possible, depending on the amount of bleeding. If the bleeding is severe, you may need a surgical procedure called a vitrectomy. During a vitrectomy, blood is removed from the center of your eye.What happens during laser treatment?

Both focal and scatter laser treatment are performed in your doctor's office or eye clinic. Before the surgery, your doctor will dilate your pupil and apply drops to numb the eye. The area behind your eye also may be numbed to prevent discomfort. The lights in the office will be dim. As you sit facing the laser machine, your doctor will hold a special lens to your eye. During the procedure, you may see flashes of light. These flashes eventually may create a stinging sensation that can be uncomfortable. You will need someone to drive you home after surgery. Because your pupil will remain dilated for a few hours, you should bring a pair of sunglasses.

For the rest of the day, your vision will probably be a little blurry. If your eye hurts, your doctor can suggest treatment.What is a vitrectomy?

If you have a lot of blood in the center of the eye (vitreous gel), you may need a vitrectomy to restore your sight. If you need vitrectomies in both eyes, they are usually done several weeks apart. A vitrectomy is performed under either local or general anaesthesia. Your doctor makes a tiny incision in your eye. Next, a small instrument is used to remove the vitreous gel that is clouded with blood. The vitreous gel is replaced with a salt solution. Because the vitreous gel is mostly water, you will notice no change between the salt solution and the original vitreous gel. You will probably be able to return home after the vitrectomy. Some people stay in the hospital overnight. Your eye will be red and sensitive. You will need to wear an eye patch for a few days or weeks to protect your eye. You also will need to use medicated eyedrops to protect against infection.Are scatter laser treatment and vitrectomy effective in treating proliferative retinopathy?

Yes. Both treatments are very effective in reducing vision loss. People with proliferative retinopathy have less than a five percent chance of becoming blind within five years when they get timely and appropriate treatment. Although both treatments have high success rates, they do not cure diabetic retinopathy. Once you have proliferative retinopathy, you always will be at risk for new bleeding. You may need treatment more than once to protect your sight.What can I do if I already have lost some vision from diabetic retinopathy?

If you have lost some sight from diabetic retinopathy, ask your eye care professional about low vision services and devices that may help you make the most of your remaining vision. Ask for a referral to a specialist in low vision. Many community organisations and agencies offer information about low vision counselling, training, and other special services for people with visual impairments. A nearby school of medicine or optometry may provide low vision services.What can I do to protect my vision?

The NEI urges everyone with diabetes to have a comprehensive dilated eye exam at least once a year. If you have diabetic retinopathy, you may need an eye exam more often. People with proliferative retinopathy can reduce their risk of blindness by 95 percent with timely treatment and appropriate followup care. A major study has shown that better control of blood sugar levels slows the onset and progression of retinopathy. The people with diabetes who kept their blood sugar levels as close to normal as

possible also had much less kidney and nerve disease. Better control also reduces the need for sight-saving laser surgery. This level of blood sugar control may not be best for everyone, including some elderly patients, children under age 13, or people with heart disease. Be sure to ask your doctor if such a control programme is right for you. Other studies have shown that controlling elevated blood pressure and cholesterol can reduce the risk of vision loss. Controlling these will help your overall health as well as help protect your vision.What should I ask my eye care professional?

You can protect yourself against vision loss by working in partnership with your eye care professional. Ask questions and get the information you need to take care of yourself and your family.

What are some questions to ask? About my eye disease or disorder...

What is my diagnosis? What caused my condition? Can my condition be treated? How will this condition affect my vision now and in the future? Should I watch for any particular symptoms and notify you if they occur? Should I make any lifestyle changes?

About my treatment...

What is the treatment for my condition? When will the treatment start and how long will it last? What are the benefits of this treatment and how successful is it? What are the risks and side effects associated with this treatment? Are there foods, drugs, or activities I should avoid while I'm on this treatment? If my treatment includes taking medicine, what should I do if I miss a dose? Are other treatments available?

About my tests...

What kinds of tests will I have? What can I expect to find out from these tests? When will I know the results? Do I have to do anything special to prepare for any of the tests? Do these tests have any side effects or risks? Will I need more tests later?

Other suggestions

If you don't understand your eye care professional's responses, ask questions until you do understand. Take notes or get a friend or family member to take notes for you. Or, bring a tape recorder to help you remember the discussion. Ask your eye care professional to write down his or her instructions to you. Ask your eye care professional for printed material about your condition. If you still have trouble understanding your eye care professional's answers, ask where you can go for more information. Other members of your health care team, such as nurses and pharmacists, can be good sources of information. Talk to them, too.

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Diabetic retinopathyFrom Wikipedia, the free encyclopedia Jump to: navigation, search Main article: Diabetes MellitusDiabetes mellitusRelated articles

Types of diabetes

Prediabetes: Impaired fasting glycaemia Impaired glucose tolerance Diabetes mellitus type 1 Diabetes mellitus type 2 Gestational diabetes

Blood tests

Blood sugar Glycosylated hemoglobin Glucose tolerance test Fructosamine

Diabetes management

Diabetic diet Anti-diabetic drugs Insulin therapy Glossary of diabetes

Complications

Cardiovascular disease Diabetic comas: Diabetic hypoglycemia Diabetic ketoacidosis Nonketotic hyperosmolar Diabetic myonecrosis Diabetic nephropathy Diabetic neuropathy Diabetic retinopathy Diabetes and pregnancy

Diabetic retinopathyClassification and external resources H36. (E10.3 E11.3 E12.3 E13.3 E14.3) 250.5

ICD-10

ICD-9

DiseasesDB 29372 MedlinePlu s eMedicine MeSH

000494 001212

oph/414 oph/415 D003930

Diabetic retinopathy is retinopathy (damage to the retina) caused by complications of diabetes mellitus, which can eventually lead to blindness. It is an ocular manifestation of systemic disease

which affects up to 80% of all patients who have had diabetes for 10 years or more[1]. Despite these intimidating statistics, research indicates that at least 90% of these new cases could be reduced if there was proper and vigilant treatment and monitoring of the eyes[2].

Normal vision. Courtesy NIH National Eye Institute

The same view with diabetic retinopathy.

Contents[hide]

1 2 3 4 5

Signs and symptoms Pathogenesis Risk factors Diagnosis Management o 5.1 Laser photocoagulation o 5.2 Panretinal photocoagulation o 5.3 Intravitreal Triamcinolone acetonide o 5.4 Vitrectomy 6 Experimental treatments o 6.1 C-peptide o 6.2 Pine bark extract 7 References 8 See also 9 External links

[edit] Signs and symptomsDiabetic retinopathy often has no early warning signs. Even macular edema, which may cause vision loss more rapidly, may not have any warning signs for some time. In general, however, a person with macular edema is likely to have blurred vision, making it hard to do things like read or drive. In some cases, the vision will get better or worse during the day. As new blood vessels form at the back of the eye as a part of proliferative diabetic retinopathy (PDR), they can bleed (hemorrhage) and blur vision. The first time this happens, it may not be very severe. In most cases, it will leave just a few specks of blood, or spots, floating in a person's visual field, though the spots often go away after a few hours. These spots are often followed within a few days or weeks by a much greater leakage of blood, which blurs vision. In extreme cases, a person will only be able to tell light from dark in that eye. It may take the blood anywhere from a few days to months or even years to clear from the inside of the eye, and in some cases the blood will not clear. These types of large hemorrhages tend to happen more than once, often during sleep. On funduscopic exam, a doctor will see cotton wool spots, flame hemorrhages (similar leisons are also caused by the alpha-toxin of Clostridium novyi), and dot-blot hemorrhages.

[edit] PathogenesisDiabetic retinopathy is the result of microvascular retinal changes. Hyperglycemia-induced intramural pericyte death and thickening of the basement membrane lead to incompetence of the

vascular walls. These damages change the formation of the blood-retinal barrier and also make the retinal blood vessels become more permeable.[3] The pericyte death is due to the "hyperglycemia persistently activates protein kinase C- (PKC-, encoded by Prkcd) and p38 mitogen-activated protein kinase (MAPK) to increase the expression of a previously unknown target of PKC- signaling, Src homology-2 domaincontaining phosphatase1 (SHP-1), a protein tyrosine phosphatase. This signaling cascade leads to PDGF receptordephosphorylation and a reduction in downstream signaling from this receptor, resulting in pericyte apoptosis..."[4] Small blood vessels such as those in the eye are especially vulnerable to poor blood sugar (blood glucose) control. An overaccumulation of glucose and/or fructose damages the tiny blood vessels in the retina. During the initial stage, called nonproliferative diabetic retinopathy (NPDR), most people do not notice any change in their vision. Some people develop a condition called macular edema. It occurs when the damaged blood vessels leak fluid and lipids onto the macula, the part of the retina that lets us see detail. The fluid makes the macula swell, which blurs vision. As the disease progresses, severe nonproliferative diabetic retinopathy enters an advanced, or proliferative, stage. The lack of oxygen in the retina causes fragile, new, blood vessels to grow along the retina and in the clear, gel-like vitreous humour that fills the inside of the eye. Without timely treatment, these new blood vessels can bleed, cloud vision, and destroy the retina. Fibrovascular proliferation can also cause tractional retinal detachment. The new blood vessels can also grow into the angle of the anterior chamber of the eye and cause neovascular glaucoma. Nonproliferative diabetic retinopathy shows up as cotton wool spots, or microvascular abnormalities or as superficial retinal hemorrhages. Even so, the advanced proliferative diabetic retinopathy (PDR) can remain asymptomatic for a very long time, and so should be monitored closely with regular checkups.

[edit] Risk factorsAll people with diabetes mellitus are at risk those with Type I diabetes (juvenile onset) and those with Type II diabetes (adult onset). The longer a person has diabetes, the higher the risk of developing some ocular problem. Between 40 to 45 percent of Americans diagnosed with diabetes have some stage of diabetic retinopathy. [5] After 20 years of diabetes, nearly all patients with type 1 diabetes and >60% of patients with type 2 diabetes have some degree of retinopathy.[6] Prior studies had also assumed a clear glycemic threshold between people at high and low risk of diabetic retinopathy.[7][8] However, it has been shown that the widely accepted WHO and American Diabetes Association diagnostic cutoff for diabetes of a fasting plasma glucose 7.0 mmol/l (126 mg/dl) does not accurately identify diabetic retinopathy among patients.[9] The cohort study included a multi-ethnic, cross-sectional adult population sample in the US, as well as two crosssectional adult populations in Australia. For the US-based component of the study, the sensitivity was 34.7% and specificity was 86.6%. For patients at similar risk to those in this study (15.8% had

diabetic retinopathy), this leads to a positive predictive value of 32.7% and negative predictive value of 87.6%. Published rates vary between trials, the proposed explanation being differences in study methods and reporting of prevalence rather than incidence values.[10] During pregnancy, diabetic retinopathy may also be a problem for women with diabetes. It is recommended that all pregnant women with diabetes have dilated eye examinations each trimester to protect their vision.[citation needed] People with Down's syndrome, who have three copies of chromosome 21, almost never acquire diabetic retinopathy. This protection appears to be due to the elevated levels of endostatin[11], an anti-angiogenic protein, derived from collagen XVIII. The collagen XVIII gene is located on chromosome 21.

[edit] DiagnosisDiabetic retinopathy is detected during an eye examination that includes:

Visual acuity test: This test uses an eye chart to measure how well a person sees at various distances (i.e., visual acuity). Pupil dilation: The eye care professional places drops into the eye to widen the pupil. This allows him or her to see more of the retina and look for signs of diabetic retinopathy. After the examination, close-up vision may remain blurred for several hours. Ophthalmoscopy: This is an examination of the retina in which the eye care professional: (1) looks through a device with a special magnifying lens that provides a narrow view of the retina, or (2) wearing a headset with a bright light, looks through a special magnifying glass and gains a wide view of the retina. Note that hand-held ophthalmoscopy is insufficient to rule out significant and treatable diabetic retinopathy. Optical coherence tomography (OCT): This is an optical imaging modality based upon interference, and analogous to ultrasound. It produces crosssectional images of the retina (B-scans) which can be used to measure the thickness of the retina and to resolve its major layers, allowing the observation of swelling and or leakage. Digital Retinal Screening Programs: Systematic programs for the early detection of eye disease including diabetic retinopathy are becoming more common, such as in the UK, where all people with diabetes mellitus are offered retinal screening at least annually. This involves digital image capture and transmission of the images to a digital reading center for evaluation and treatment referral. See Vanderbilt Ophthalmic Imaging Center [1] and the English National Screening Programme for Diabetic Retinopathy [2] Slit Lamp Biomicroscopy Retinal Screening Programs: Systematic programs for the early detection of diabetic retinopathy using slit-lamp biomicroscopy. These exist either as a standalone scheme or as part of the Digital program (above) where the digital photograph was considered to lack enough clarity for detection and/or diagnosis of any retinal abnormality.

The eye care professional will look at the retina for early signs of the disease, such as: (1) leaking blood vessels, (2) retinal swelling, such as macular edema, (3) pale, fatty deposits on the retina (exudates) signs of leaking blood vessels, (4) damaged nerve tissue (neuropathy), and (5) any changes in the blood vessels. Should the doctor suspect macular edema, he or she may perform a test called fluorescein angiography. In this test, a special dye is injected into the arm. Pictures are then taken as the dye passes through the blood vessels in the retina. This test allows the doctor to find the leaking blood vessels.

[edit] ManagementThere are three major treatments for diabetic retinopathy, which are very effective[citation needed] in reducing vision loss from this disease. In fact, even people with advanced retinopathy have a 90 percent chance of keeping their vision when they get treatment before the retina is severely damaged. These three treatments are laser surgery, injection of triamcinolone into the eye and vitrectomy. It is important to note that although these treatments are very successful, they do not cure diabetic retinopathy. Caution should be exercised in treatment with laser surgery since it causes a loss of retinal tissue. It is often more prudent to inject triamcinolone. In some patients it results in a marked increase of vision, especially if there is an edema of the macula. Avoiding tobacco use and correction of associated hypertension are important therapeutic measures in the management of diabetic retinopathy. [12] The best way of addressing diabetic retinopathy is to monitor it vigilantly. By 2008 there were other drugs (eg kinase inhibitors and anti-VEGF) available.[13][edit] Laser photocoagulation

Laser photocoagulation can be used in two scenarios for the treatment of diabetic retinopathy. It is widely used for early stages of proliferative retinopathy.[edit] Panretinal photocoagulation

Panretinal photocoagulation, or PRP (also called scatter laser treatment), is used to treat proliferative diabetic retinopathy (PDR). The goal is to create 1,000 - 2,000 burns in the retina with the hope of reducing the retina's oxygen demand, and hence the possibility of ischemia. In treating advanced diabetic retinopathy, the burns are used to destroy the abnormal blood vessels that form in the retina. This has been shown to reduce the risk of severe vision loss for eyes at risk by 50%.[14]

Before the laser, the ophthalmologist dilates the pupil and applies anesthetic drops to numb the eye. In some cases, the doctor also may numb the area behind the eye to prevent any discomfort.

The patient sits facing the laser machine while the doctor holds a special lens to the eye. The physician can use a single spot laser or a pattern scan laser for two dimensional patterns such as squares, rings and arcs. During the procedure, the patient may see flashes of light. These flashes may eventually create an uncomfortable stinging sensation for the patient. After the laser treatment, patients should be advised not to drive for a few hours while the pupils are still dilated. Vision may remain a little blurry for the rest of the day, though there should not be much pain in the eye. Patients may lose some of their peripheral vision after this surgery, but the procedure saves the rest of the patient's sight. Laser surgery may also slightly reduce colour and night vision. A person with proliferative retinopathy will always be at risk for new bleeding, as well as glaucoma, a complication from the new blood vessels. This means that multiple treatments may be required to protect vision.[edit] Intravitreal Triamcinolone acetonide

Triamcinolone is a long acting steroid preparation. When injected in the vitreous cavity, it decreases the macular edema (thickening of the retina at the macula) caused due to diabetic maculopathy, and results in an increase in visual acuity. The effect of triamcinolone is transient, lasting up to three months, which necessitates repeated injections for maintaining the beneficial effect. Complications of intravitreal injection of triamcinolone include cataract, steroid-induced glaucoma and endophthalmitis.[edit] Vitrectomy

Instead of laser surgery, some people require a vitrectomy to restore vision. A vitrectomy is performed when there is a lot of blood in the vitreous. It involves removing the cloudy vitreous and replacing it with a saline solution. Studies show that people who have a vitrectomy soon after a large hemorrhage are more likely to protect their vision than someone who waits to have the operation. Early vitrectomy is especially effective in people with insulin-dependent diabetes, who may be at greater risk of blindness from a hemorrhage into the eye. Vitrectomy is often done under local anesthesia. The doctor makes a tiny incision in the sclera, or white of the eye. Next, a small instrument is placed into the eye to remove the vitreous and insert the saline solution into the eye. Patients may be able to return home soon after the vitrectomy, or may be asked to stay in the hospital overnight. After the operation, the eye will be red and sensitive, and patients usually need to wear an eyepatch for a few days or weeks to protect the eye. Medicated eye drops are also prescribed to protect against infection.

[edit] Experimental treatments[edit] C-peptide

Though not yet commercially available, c-peptide has shown promising results in treatment of diabetic complications incidental to vascular degeneration. Once thought to be a useless byproduct of insulin production, it helps to ameliorate and reverse many symptoms of diabetes[15].[edit] Pine bark extract

A pine bark extract of oligomeric proanthocyanidins has been shown to improve microcirculation, retinal edema and visual acuity in the early stages of diabetic retinopathy[16].

[edit] References1. ^ PJ Kertes, TM Johnson Eds. Evidence Based Eye Care (c) 2007 2. ^ Tapp, R. et al (2003) The prevalence of and factors associated with diabetic retinopathy in the Australian population. Diabetes care. 26(6), pg. 1371. 3. ^ Understanding diabetic retinopathy by Pardianto G et al., in Mimbar Ilmiah Oftalmologi Indonesia.2005;2: 65-6. 4. ^ http://www.nature.com/nm/journal/v15/n11/full/nm.2052.html "Activation of PKC- and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy" 2009 5. ^ "NIHSeniorHealth: Diabetic Retinopathy - Causes and Risk Factors". Diabetic Retinopathy. NIHSenior Health. 2005. http://nihseniorhealth.gov/diabeticretinopathy/causesandriskfactors/02.html. 6. ^ "Screening for Diabetic Retinopathy". Diabetic Retinopathy. American Diabetes Association. 2002. http://care.diabetesjournals.org/cgi/content/full/25/suppl_1/s90. 7. ^ "Report of the expert committee on the diagnosis and classification of diabetes mellitus". Diabetes Care 26 Suppl 1: S520. 2003. PMID 12502614. http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=12502614. 8. ^ "Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus". Diabetes Care 20 (7): 118397. 1997. PMID 9203460. 9. ^ Wong TY, Liew G, Tapp RJ, et al. (2008). "Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based crosssectional studies". Lancet 371 (9614): 73643. doi:10.1016/S01406736(08)60343-8. PMID 18313502. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)60343-8. 10.^ Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A (2004). "Epidemiology of diabetic retinopathy and macular oedema: a systematic review". Eye 18 (10): 96383. doi:10.1038/sj.eye.6701476. PMID 15232600. 11.^ http://journals.lww.com/jcraniofacialsurgery/Abstract/2009/03001/Role_of_Endo genous_Angiogenesis_Inhibitors_in_Down.9.aspx 12.^ "Diabetes Ocular complications". Chronic Complications of Diabetes. Armenian Medical Network. 2006. http://www.health.am/db/diabetes-ocularcomplications/.

13.^ http://www.ncbi.nlm.nih.gov/pubmed/18408491? ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pu bmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews &logdbfrom=pubmed 14.^ PJ Kertes TM Johnson, Eds, Evidence-Based Eye Care (C)2007 15.^ Wahren, J., Ekberg, K., & Jrnval, H. 2007. C-peptide is a bioactive peptide. Diabetologia. Volume 50, Number 3 16.^ http://www.eurekalert.org/pub_releases/2009-12/mg-ssp113009.php "Study shows pine bark improves circulation, swelling and visual acuity in early diabetic retinopathy" Dec 2009

The original text of this document was taken from the public domain resource document "Facts About Diabetic Retinopathy", at http://www.nei.nih.gov/health/diabetic/retinopathy.asp See the copyright statement at http://www.nei.nih.gov/order/index.htm, which says "Our publications are not copyrighted and may be reproduced without permission. However, we do ask that credit be given to the National Eye Institute, National Institutes of Health."

[edit] See also

PERSPECTIVE

Diabetic retinopathy in pregnancyR M Best, U ChakravarthyDiabetic retinopathy is one of the major causes of preventable blindness in the UK and USA in those aged between 24 and 64 years.1 For a proportion of diabetic women, the first half of this period coincides with peak fertility and childbearing years. Diabetic eye disease may develop for the first time during pregnancy, and visual loss at this stage has serious implications for both the patient and her family. In the past, the prognosis for pregnancy in diabetic women with microvascular disease was so poor that many physicians advised avoidance or termination of pregnancy. 2 With the recognition that the level of glycaemia during pregnancy is directly related to the incidence of congenital malformations, the emphasis on the management of diabetic pregnancy has been one of meticulous control of blood sugar and this has undoubtedly resulted in lower rates of fetal malformations. However, intensive control of glycaemia may carry risks to diabetic mothers particularly to those with established microvascular diseases such as retinopathy and nephropathy. Studies on the influence of pregnancy on the natural history of diabetic retinopathy have shown that deterioration is frequently observed. 3 4 Until recently there has been controversy as to whether the progression of retinopathy which occurs in such women is due to the natural tendency of diabetic retinopathy to worsen or to unique factors operative during pregnancy. Several major studies have gone some way towards explaining the mechanisms underlying

progression of retinopathy during pregnancy. Klein et al performed a prospective study on a large series of individuals, comprising 171 pregnant and 298 non-pregnant insulin dependent diabetic women. 5 The level of diabetic retinopathy in the first trimester was assessed using standard retinal photographs and compared with postpartum photographs. After adjusting for duration of diabetes, glycaemic control, and blood pressure current pregnancy was found to be a major risk factor for the progression of retinopathy. 5 Similarly, Moloney and Drury, also using retinal photography as a means of assessing retinopathy, found that current pregnancy in 53 pregnant diabetic women was associated both with an increased prevalence (from 62% to 77%) and severity of retinopathy whereas in the control group of 39 non-pregnant diabetic women the prevalence of retinopathy remained unchanged at 46% throughout the study period.3 That retinopathy worsens during pregnancy is now undisputed, although the mechanism by which progression occurs is not entirely clear. Risk factors for the progression of retinopathy in pregnancyMETABOLIC CONTROL

An elegant study by Phelps et al 6 monitored changes in diabetic retinopathy status during pregnancy and correlated these findings with blood sugar measurements made at corresponding time points. These findings were further supported and extended by the Diabetes in Early Pregnancy Study (DIEP), 7 a prospective cohort study on 140 pregnant diabetic women who were followed from early pregnancy to delivery using retinal photography. It was clearly shown that those women with the greatest reduction in glycosylated haemoglobin (HbA1c) over the first 14 weeks of pregnancy were at an increased risk of progression of retinopathy. 7 Patients in whom retinopathy was most likely to progress had both the poorest control at baseline and the largest improvement during early pregnancy. However, it was impossible to separate these two risk factors as virtually all patients had improved metabolic control during early pregnancy.DURATION OF DIABETES

Another risk factor which has been shown to adversely influence progression of retinopathy is the duration of diabetes before pregnancy. 8 Dibble et al followed 55 insulin dependent diabetic women through their pregnancies and found a positive correlation between duration of diabetes and progression of retinopathy. 8 However, the results of the more recent and larger DIEP study suggest that duration of diabetes is probably not as important a risk factor for any change in retinopathy as baseline severity of retinopathy. Retinopathy was noticed to progress by two or more steps in 55% of patients with less than 15 years of disease and 50% of those with more than 15 years of disease and these differences were not significant. 7 But, when the rate of development of retinopathy was compared in patients stratified by duration of diabetes, retinopathy progressed to proliferative levels in 39% of patients with more than 15 years of diabetes as opposed to 18% of patients with a disease duration of less than 15 years.7 These findings indicate that duration of diabetes, which is strongly correlated with level of baseline retinopathy, may be a significant factor in the development of more severe changethat is, proliferative

retinopathy in pregnancy.BASELINE SEVERITY OF RETINOPATHY

It has been shown that risk of visual loss is low in those with no pre-existing retinopathy. Approximately 12% of women with no retinopathy at the start of pregnancy will develop minor background retinopathy consisting of a few microaneurysms but regression in the postpartum period is the norm.9 Using fluorescein angiography Soubrane et al showed that in women with mild background diabetic retinopathy the number of retinal microaneurysms increased progressively during pregnancy but underwent substantial regression postpartum though not quite returning to preconception levels.10 On the other hand when pre-existing retinopathy is more severe, proliferative changes can develop in a significant number of cases. Thus in the DIEP study, 29% of patients whose fundal appearance was classified as showing moderate retinopathy at baseline went on to develop proliferative changes during pregnancy. This was in contrast with those women who had minimal retinopathy at baseline where only 6.3% progressed to the proliferative category. 7 These findingsBritish Journal of Ophthalmology 1997;81:249251 249

indicate that severity of existing diabetic retinopathy profoundly influences the level of progression.RETINAL BLOOD FLOW

Pregnancy is associated with major changes in the systemic vasculature. There is an augmentation in cardiac output and plasma volume and a decrease in peripheral resistance, all of which cause increased blood flow. Chen et al, using laser Doppler velocimetry to measure retinal blood flow, demonstrated the lack of change of retinal blood flow in normal pregnancy, thus confirming the efficacy of the autoregulatory processes in the retinal vasculature. 11 In diabetic patients who showed progression of retinopathy in pregnancy, an increase in blood flow was documented in the first trimester. By contrast, women with diabetes whose retinal blood flow remained unchanged developed no retinopathy. 11 They therefore suggested that the hyperdynamic circulatory state of early pregnancy is accompanied by compensatory mechanisms both in normal women and in those diabetes sufferers who retain autoregulatory control of retinal blood flow. In some diabetic women, however, these autoregulatory mechanisms are flawed resulting in an increase in blood flow. Such a hyperdynamic circulatory state could potentially inflict additional shear stress and cause endothelial damage particularly at the capillary level.12 However, local hypoxia associated with worsening retinopathy could account for the compensatory increase in blood flow which may merely represent an epiphenomenon rather than failure of autoregulation in pregnancy.HYPERTENSION

Hypertension is a known risk factor for the progression of retinopathy and is additionally hazardous during pregnancy. 5 13 Rosenn et al followed 154 insulin dependent diabetic women throughout their pregnancies of whom approximately a third had either chronic hypertension or pregnancy induced hypertension or both. Fifty five per cent of those with a hypertensive disorder developed progression of retinopathy as opposed to 25% of those that did not.13 Pharmacological treatment of hypertension in pregnancy is most suitable for early onset, severe disease when an attempt to delay delivery is indicated and methyldopa,

blockers, and vasodilators have been used with some success.14 A recent report has indicated that treatment of women with diabetes with the angiotensin converting enzyme (ACE) inhibitor captopril for 6 months before the onset of pregnancy reduces proteinuria, improves renal function, and is associated with favourable maternal and fetal outcome. 15 In at least one major study all patients with severe proliferative retinopathy also had proteinuria indicating a generalised vasculopathy. 6 Thus, it is not inconceivable that functional improvement in one circulatory bed might be mirrored in others. However, the use of ACE inhibitors during pregnancy is not recommended as they are extremely fetotoxic resulting in hypotension, renal tubular dysplasia, anuriaoligohydramnios, growth restriction, and death of the fetus.16 Nevertheless, clinical studies of ACE inhibitors in diabetic retinopathy carried out before the onset of pregnancy might well be worthwhile. Fundus changes in diabetic retinopathy in pregnancy Cotton wool spots develop in a proportion of patients with background retinopathy as pregnancy advances and have been seen to be associated with low fasting blood sugar. 3 As hypoglycaemia often occurs in the wake of institution of rapid metabolic control,6 it has been suggested that low plasma glucose may be responsible for the retinal hypoxia and damage.3 These morphological alterations are not dissimilar to those observed in non-gravid diabetic individuals who may experience transient worsening of retinopathy when subjected to strict glycaemic control in whom the major changes are cotton wool spots and intraretinal microvascular abnormalities.17 However, Phelps et al 6 have reported that the components of retinopathy which increased most commonly in pregnancy were haemorrhages and microaneurysms, suggesting that there may be differences in pathophysiological aetiology between gravid and non-gravid subjects. Effect of diabetic retinopathy on pregnancy Increasing severity of diabetic retinopathy has been shown to adversely affect outcome in pregnancy. Price et al retrospectively reviewed 23 pregnancies in insulin dependent diabetics who had had serial retinal examinations during pregnancy. 18 They noted that 30% of patients who had no observable retinopathy and 70% of patients with background retinopathy at the inception of pregnancy developed obstetric complications. It was noteworthy that all of those with proliferative retinopathy at the start of pregnancy developed pregnancy induced hypertension or other obstetric complications.18 In another study the impact of diabetic retinopathy on pregnancy was examined in 179 women with diabetes.19 The pregnancies in 43% of the women with proliferative retinopathy had an unfavourable outcome compared with 13% of those with nonproliferative or no retinopathy and, overall, a fifth of the pregnancies resulted in fetuses with severe congenital malformations and/or fetal death. 19 Thus, severity of retinopathy at baseline was strongly predictive of an adverse outcome in these patients. Long term consequences of pregnancy on diabetic retinopathy In an attempt to determine whether pregnancy had an

unfavourable effect on retinopathy in the long term Klein and Klein investigated the severity of retinopathy in two groups of diabetic women, one of which had experienced pregnancy and the other had never been pregnant. 20 No difference was observed in severity of retinopathy between the groups suggesting the absence of any deleterious effects attributable to pregnancy. 20 These findings have been supported by other studies which have shown no long term detrimental effects due to pregnancy in other organs such as the kidney or peripheral nervous system. 21 22 Conversely, retinopathy of less overall severity in parous women has been reported,21 and the rigorous and intensive control of diabetes instituted during pregnancy in these women has been cited as having a possible protective effect in the long term. Management of diabetic retinopathy in pregnancy Before the advent of laser photocoagulation, proliferative retinopathy was a contraindication to pregnancy because of the substantial risk of severe visual loss, so that women with diabetes who became pregnant were advised to consider termination.2 With the use of laser photocoagulation and the establishment and recognition of high risk characteristics23 the likelihood of visual loss has been reduced. Progression of proliferative retinopathy may depend upon whether or not laser photocoagulation has been carried out before pregnancy. One study of patients with proliferative retinopathy detected in early pregnancy and subsequently treated by laser showed that 58% experienced significant progression and visual loss.9 On the other hand only 26% of patients in whom retinopathy was diagnosed and treated before onset of pregnancy showed progression of retinopathy during an ensuing gestation250 Best, Chakravarthy

period.9 The indications for treatment and the response to laser photocoagulation are exactly the same as for other diabetes sufferers.24 Nevertheless, some studies have found that vascular proliferation is reversible and postpartum regression is common,25 and currently therefore most ophthalmologists would perform a restricted or limited photocoagulation procedure. However, there are a group of women in whom retinopathy is aggressive, responds poorly to photocoagulation, and continues to progress postpartum. 26 Thus, it is important that proliferative retinopathy is detected and treated preferably before the onset of pregnancy. Those who develop proliferative retinopathy during pregnancy should have prompt laser photocoagulation treatment sufficient to induce regression. Sinclair et al 27 have identified a group of insulin dependent diabetics who developed macular oedema in pregnancy and who also typically developed proteinuria and mild hypertension concomitantly. Laser photocoagulation may be required to treat macular changes but this in itself can exacerbate the oedema particularly in those with a compromised macular capillary circulation. Alternative therapies for this condition include salt restriction diets and diuretics which have been used with limited success. 28 When macular oedema occurs it is thought to be due to an ischaemic capillaropathy and may be accompanied by proliferative retinopathy. In some cases macular oedema regresses postpartum but in others it may persist and cause long term visual loss.27 Generally, the diagnosis of sight

threatening retinopathy is made on ophthalmoscopic appearances. However, fluorescein angiography is a more sensitive tool to assess the extent of capillary non-perfusion and early neovascularisation and may be of value in the management of pregnant diabetics particularly since there is no evidence that it has any detrimental effect on the developing fetus.29 Despite the tendency for retinopathy to worsen after the institution of strict glycaemic control, there is an overall strong beneficial effect of near normoglycaemia which includes a reduction of retinopathy by 50% at 2 years of follow up.30 31 It is also recognised that normalisation of blood sugar during pregnancy is the most important factor for the successful outcome of pregnancy in diabetes, 32 33 as a high rate of preterm deliveries (39%) and frequent occurrence of intrauterine growth retardation (9%) characterise the fetal outcome in women with uncontrolled diabetes.34 It is therefore recommended that diabetic women who are contemplating pregnancy and who are suboptimally controlled (glycosylated haemoglobin > 6 SD above the control mean) should be targeted for the institution of strict glycaemic control.7 Ideally, young women with diabetes should be seen for counselling and management before the onset of pregnancy. Although studies suggest that most patients recognise the value of good blood glucose control,35 a significant proportion may be unaware of the potential risks to vision. In summary, progression of retinopathy in pregnancy depends on a variety of factors including severity of retinopathy at conception, adequacy of treatment, duration of diabetes, metabolic control before pregnancy, and the presence of additional vascular damage such as preexisting or concomitant hypertensive disorder. The risks of visual loss in those with minimal retinopathy at the inception of pregnancy are minor, and for these mothers a fundus examination every 3 months should suffice. In those with moderate background retinopathy, funduscopy should be performed at each obstetric visit (which is usually every 4 to 6 weeks) and if progression is detected the patient should be examined at 2 week intervals to detect any high risk characteristics. If high risk characteristics develop photocoagulation should be carried out promptly and monitored by funduscopy. In those with severe sight threatening retinopathy, laser photocoagulation should be performed before pregnancy or promptly when high risk characteristics develop.R M BEST U CHAKRAVARTHY Department of Ophthalmology, Queens University of Belfast, Royal Victoria Hospital, Belfast BT12 6BA1 Kohner EM, Porta M. Protocols for screening and treatment of diabetic retinopathy in Europe. Eur J Ophthalmol 1991;1:4554. 2 White P. Diabetes mellitus in pregnancy. Clin Perinatol 1974;1:33147. 3 Moloney JB, Drury MI. The effect of pregnancy on the natural course of diabetic retinopathy. Am J Ophthalmol 1982;93:74556. 4 Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. III Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 1984;102:52732. 5 Klein BE, Moss SE, Klein R. Effect of pregnancy on progression of diabetic retinopathy. Diabetes Care 1990;13:3440. 6 Phelps RL, Sakol P, Metzger BE, Jampol LM, Freinkel N. Changes in diabetic retinopathy during pregnancy. Correlations with regulation of hyperglycemia. Arch Ophthalmol 1986;104:180610. 7 Diabetes in Early Pregancy Study. Metabolic control and progression of retinopathy. Diabetes Care 1995;18:6317. 8 Dibble CM, Kochenour NK, Worley RJ, Tyler FH, Swartz M. Effect of

pregnancy on diabetic retinopathy. Obstet Gynecol 1982;59:699704. 9 Sunness JS. The pregnant womans eye. Surv Ophthalmol 1988;32:21938. 10 Soubrane G, Canivet J, Coscas G. Influence of pregnancy on the evolution of background retinopathy. Preliminary results of a prospective fluorescein angiography study. Inte Ophthalmol 1985;8:24955. 11 Chen HC, Newsom RS, Patel V, Cassar J, Mather H, Kohner EM. Retinal blood flow changes during pregnancy in women with diabetes. Invest Ophthalmol Vis Sci 1994;35:3199208. 12 Tooke JE. Microvascular function in human diabetes. A physiological perspective. Diabetes 1995;44:7216. 13 Rosenn B, Miodovnik M, Kranias G, Khoury J, Combs CA, Mimouni F, et al Progression of diabetic retinopathy in pregnancy: association with hypertension in pregnancy. Am J Obstet Gynecol 1992;166:12148. 14 Erman A, Boner G, Ovadia J. Diabetic nephropathy and pregnancy. The effect of ACE inhibitors prior to pregnancy on fetomaternal outcome. Nephrol Dial Transplant 1995;10:232833. 15 Pipkin FB, Rubin PC. Pre-eclampsiathe disease of theories. Br Med Bull 1994;50:38196. 16 Sedman AB, Kershaw DB, Bunchman TE. Recognition and management of angiotensin-converting enzyme-inhibitor. Pediatr Nephrol 1995;9:3825. 17 KROC collaborative study group. Blood glucose control and the evolution of diabetic retinopathy and albuminuria. N Engl J Med 1984;311:36572. 18 Price JH,Hadden DR, Archer DB, Harley JM.Diabetic retinopathy in pregnancy. Br J Obstet Gynaecol 1984;91:117. 19 Klein BE, Klein R, Meuer SM, Moss SE, Dalton DD. Does the severity of diabetic retinopathy predict pregnancy outcome? J Diabet Complications 1988;2:17984. 20 Klein BE, Klein R. Gravidity and diabetic retinopathy. Am J Epidemiol 1984;119:5649. 21 Chaturvedi N, Stephenson JM, Fuller JH. The relationship between pregnancy and long-term maternal complications in the EURODIAB IDDM Complications Study. Diabetic Med 1995;12:4949. 22 Hemachandra A, Ellis D, Lloyd CE, Orchard TJ. The influence of pregnancy on IDDM complications. Diabetes Care 1995;18:9504. 23 Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV Ten-year incidence and progression of diabetic retinopathy [see comments]. Arch Ophthalmol 1994; 112:121728. 24 Hercules BL,Wozencroft M, Gayed II, Jeacock J. Peripheral retinal ablation in the treatment of proliferative diabetic retinopathy during pregnancy. Br J Ophthalmol 1980;64:8793. 25 Serup L. Influence of pregnancy on diabetic retinopathy. Acta Endocrinol 1994;27(Suppl 1986):1224. 26 Conway M, Baldwin J, Kohner EM, Schulenburg WE, Cassar J. Postpartum progression of diabetic retinopathy. Diabetes Care 1991;14:11101. 27 Sinclair SH, Nesler C, Foxman B, Nichols CW, Gabbe S. Macular edema and pregnancy in insulin-dependent diabetes. Am J Ophthalmol 1984;97: 15467. 28 Cassar J, Hamilton AM, Kohner EM. Diabetic retinopathy in pregnancy. Int Ophthalmol Clin 1978;18:17988. 29 Halperin LS, Olk RJ, Soubrane G, Coscas G. Safety of fluorescein angiography during pregnancy. Am J Ophthalmol 1990;109:5636. 30 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:97786. 31 Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in in insulin-dependent diabetes mellitus. Arch Ophthalmol 1995;113:3651. 32 Reid M, Hadden D, Harley JMG, Halliday HL, McClure BG. fetal malformations in diabetics with high haemoglobin A1c in early pregnancy. BMJ 1984;289:1001. 33 Jovanovic R, Jovanovic L. Obstetric management when normoglycemia is maintained in iabetic pregnant women with vascular compromise. Am J Obstet Gynecol 1984;149:61723. 34 Hopp H, Vollert W, Weitzel H, Glockner E, Jahrig D. Diabetic retinopathy and nephropathy. Complications during pregnancy and delivery. Geburtshilfe und Frauenheilkunde 1995;55:2759. 35 Gibb D, Hockey S, Brown LJ, Lunt H. Attitudes and knowledge regarding contraception and prepregnancy. NZ Med J 1994;107:4846.

Diabetic retinopathy in pregnancy 251

Diabetes Mellitus in Pregnancy (Gestational Diabetes)

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(See also Diabetes Mellitus and Disorders of Carbohydrate Metabolism) Pregnancy aggravates preexisting type 1 (insulin-dependent) and type 2 (non insulin-dependent) diabetes but does not appear to exacerbate diabetic retinopathy, nephropathy, or neuropathy. Gestational diabetes (diabetes that begins during pregnancy) can develop in overweight, hyperinsulinemic, insulin-resistant women or in thin, relatively insulin-deficient women. Gestational diabetes occurs in 1 to 3% of all pregnancies, but the rate may be much higher in certain groups (eg, Mexican Americans, American Indians, Asians, Indians, Pacific Islanders). Diabetes during pregnancy increases fetal and maternal morbidity and mortality. Neonates are at risk of respiratory distress, hypoglycemia, hypocalcemia, hyperbilirubinemia, polycythemia, and hyperviscosity. Poor control of preexisting or gestational diabetes during organogenesis (up to about 10 wk gestation) increases risk of major congenital malformations and spontaneous abortion. Poor control of diabetes later in pregnancy increases risk of fetal macrosomia (usually defined as fetal weight > 4000 or > 4500 g at birth), preeclampsia, and spontaneous abortion. However, gestational diabetes can result in fetal macrosomia even if plasma glucose is kept nearly normal. Treatment

Close monitoring Tight control of plasma glucose Management of complications

Preconception counseling and optimal control of diabetes before, during, and after pregnancy minimize maternal and fetal risks, including congenital malformations. Because malformations may develop before pregnancy is diagnosed, the need for constant, strict control of glucose levels is stressed to women who have diabetes

and who are considering pregnancy (or who are not using contraception). Most experts recommend that all pregnant women be screened for gestational diabetes. A glucose tolerance test is usually recommended, but the diagnosis can probably be made by a fasting plasma glucose of > 126 mg/dL or a random plasma glucose > 200 mg/dL (see Approach to the Pregnant Woman and Prenatal Care: Laboratory testing). To minimize risks, clinicians should do all of the following:

Involve a diabetes team (eg, physicians, nurses, nutritionists, social workers) and a pediatrician Promptly diagnose and treat complications of pregnancy, no matter how trivial Plan for delivery and have an experienced pediatrician present Ensure that neonatal intensive care is available

In regional perinatal centers, specialists in management of diabetic complications are available. During pregnancy: Treatment can vary, but some general management guidelines are useful (see Table 1: Pregnancy Complicated by Disease: Management of Type 1 Diabetes Mellitus* During Pregnancy , Table 2: Pregnancy Complicated by Disease: Management of Type 2 Diabetes Mellitus* During Pregnancy , and Table 3: Pregnancy Complicated by Disease: Management of Gestational Diabetes During Pregnancy ). Women with type 1 or 2 should monitor their plasma glucose levels at home. During pregnancy, normal fasting plasma glucose levels are about 76 mg/dL (4.2 mmol/L); treatment aims to keep fasting plasma glucose levels at < 95 mg/dL (5.3 mmol/L) and 2-h postprandial levels at 120 mg/dL ( 6.6 mmol/L). The goals are no wide plasma glucose fluctuations and glycosylated Hb (Hb A1c) levels kept at < 8%. Table 1 Management of Type 1 Diabetes Mellitus* During Pregnancy Time Frame Measures Before conception Diabetes is controlled. Risk is lowest if Hb A1c levels are 8% at conception. Evaluation includes

24-h urine collection (protein excretion and creatinine clearance) to check for renal complications Ophthalmologic examination to check for

retinal complications Prenatal ECG to check for cardiac complications Prenatal visits begin as soon as pregnancy is recognized. Frequency of visits is determined by degree of glycemic control.

Diet should be individualized according to ADA guidelines and coordinated with insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph administration. Three meals and 3 snacks/day are recommended, with emphasis on consistent timing. Women are instructed in and should do plasma glucose self-monitoring. Women should be cautioned about the dangers of hypoglycemia during exercise and at night. Women and their family members should be instructed in glucagon administration. Hb A1c level should be checked every trimester. Fetal monitoring with the following should be done weekly from 32 wk to delivery (or earlier if indicated):

Nonstress tests Biophysical profiles Kick counts

Amount and type of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph should be individualized. In the am; 2/3 of total dose (60% NPH, 40% regular) is taken; in the pm; 1/3 (50% NPH, 50% regular) is taken. During labor and delivery Vaginal delivery at term is possible if women have documented dating criteria and good glycemic control.

Amniocentesis is not done unless indicated for another problem or requested by the couple. Cesarean delivery should be reserved for obstetrical indications or fetal macrosomia (>4500 g), which increases risk of shoulder dystocia. Delivery should occur by 38-40 wk. During delivery, a constant low-dose insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph infusion is usually preferred, and the usual sc administration of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph is stopped. If induction is planned, the usual PM NPH insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph dose is given on the day before induction. Postpartum and continuing diabetes care should be arranged. Postpartum insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph requirements may decrease by up to 50%. * Guidelines are only suggested; marked individual variations require appropriate adjustments. Normal values may differ depending on laboratory methods used. Some hospital programs recommend up to 4 insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph injections daily. Continuous sc insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph

infusion, which is labor-intensive, can sometimes be given in specialized diabetic research settings. ADA = American Diabetes Association; Hb A1c = glycosylated Hb; NPH = neutral protamine Hagedorn. Table 2 Management of Type 2 Diabetes Mellitus* During Pregnancy Time Frame Measures Before conception Hyperglycemia is controlled. Risk is lowest if Hb A1c levels are 8% at conception. Weight loss is encouraged if BMI is >27 kg/m2. The diet should be low in fat, relatively high in complex carbohydrates, and high in fiber. Prenatal Exercise is encouraged. For overweight women, diet and caloric intake are individualized and monitored to avoid weight gain of >9 kg; daytime snacks are discouraged. Moderate walking after meals is recommended. Women are instructed in and should do plasma glucose self-monitoring. The 2-h postbreakfast plasma glucose level is checked weekly at clinic visits. Hb A1c level should be checked every trimester. Fetal monitoring with the following should be done weekly from 32 wk to delivery (or earlier if indicated):

Nonstress tests Biophysical profiles Kick counts

Amount and type of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph is individualized. For obese women, regular insulin Some Trade Names HUMULIN NOVOLIN

Click for Drug Monograph is taken before each meal. For women who are not obese, 2 /3 of total dose (60% NPH, 40% regular) is taken in the am; 1/3 (50% NPH, 50% regular) is taken in the pm. During labor and Management is the same as for type 1 (see Table 1: delivery Pregnancy Complicated by Disease: Management of Type 1 Diabetes Mellitus* During Pregnancy ). * Guidelines are only suggested; marked individual variations require appropriate adjustments. Normal values may differ depending on laboratory methods used. BMI = body mass index; Hb A1c = glycosylated Hb; NPH = neutral protamine Hagedorn. Table 3 Management of Gestational Diabetes During Pregnancy Time Frame Measures Before conception Women who have had gestational diabetes in previous pregnancies should try to reach a normal weight and engage in modest exercise. The diet should be low in fat, relatively high in complex carbohydrates, and high in fiber. Fasting plasma glucose and Hb A1c levels should be checked. Diet and caloric intake are individualized and monitored to prevent weight gain of >9 kg. Obese women are discouraged from daytime snacks. Moderate exercise after meals is recommended. Fetal monitoring with the following should be done weekly from 32 wk to delivery (or earlier if indicated):

Prenatal

Nonstress tests Biophysical profiles Kick counts

Insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph therapy is reserved for persistent hyperglycemia (fasting plasma glucose >95 mg/dL or 2-h postprandial plasma glucose >120 mg/dL) despite a trial of dietary therapy

for 2 wk. The amount and type of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph should be individualized. For obese women, regular insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph is taken before each meal. For women who are not obese, 2/3 of total dose (60% NPH, 40% regular) is taken in the am; 1/3 (50% NPH, 50% regular) is taken in the pm. During labor and delivery Vaginal delivery at term is possible if women have a well-documented delivery date and good diabetic control. Amniocentesis may not be required. Cesarean delivery should be reserved for obstetric indications or fetal macrosomia (>4500 g), which increases risk of shoulder dystocia. Delivery should occur by 38-40 wk. Hb A1c = glycosylated Hb; NPH = neutral protamine Hagedorn. Insulin is the traditional drug of choice because it cannot cross the placenta and provides more predictable glucose control; it is used for types 1 and 2 diabetes and for some women with gestational diabetes. Human insulin is used if possible because it minimizes antibody formation. Insulin antibodies cross the placenta, but their effect on the fetus is unknown. In some women with long-standing type 1 diabetes, hypoglycemia does not trigger the normal release of counterregulatory hormones (catecholamines, glucagon, cortisol, and growth hormone); thus, too much insulin can trigger hypoglycemic coma without premonitory symptoms. All pregnant women with type 1 should have glucagon kits and be instructed (as should family members) in giving glucagon if severe hypoglycemia (indicated by unconsciousness, confusion, or plasma glucose levels < 40 mg/dL [< 2.2 mmol/L]) occurs. Oral hypoglycemic drugs (eg, glyburide Some Trade Names DIABETA GLYNASE MICRONASE

Click for Drug Monograph ) are being increasingly used to manage diabetes in pregnant women because of the ease of administration (pills compared to injections), low cost, and single daily dosing. Several studies have demonstrated that glyburide Some Trade Names DIABETA GLYNASE MICRONASE Click for Drug Monograph is safe during pregnancy and that it provides control equivalent to that of insulin for women with gestational diabetes. For women with type II diabetes before pregnancy, data for oral drugs are scant; insulin is most often preferred. Oral hypoglycemics taken during pregnancy may be continued postpartum during breastfeeding, but the infant should be closely monitored for signs of hypoglycemia. Management of complications: Although diabetic retinopathy, nephropathy, and mild neuropathy do not contraindicate pregnancy, they require preconception counseling and close management before and during pregnancy. Retinopathy requires that an ophthalmologic examination be done every trimester. If proliferative retinopathy is noted at the first prenatal visit, photocoagulation should be used as soon as possible to prevent progressive deterioration. Nephropathy, particularly in women with renal transplants, predisposes to pregnancy-induced hypertension. Risk of preterm delivery is higher if maternal renal function is impaired or if transplantation was recent. Prognosis is best if delivery occurs 2 yr after transplantation. Congenital malformations of major organs are predicted by elevated Hb A1c levels at conception and during the first 8 wk of pregnancy. If the level is 8.5% during the 1st trimester, risk of congenital malformations is significantly increased, and targeted ultrasonography and fetal echocardiography are done during the 2nd trimester to check for malformations. If women with type 2 diabetes take oral hypoglycemic drugs during the 1st trimester, fetal risk of congenital malformations is unknown (see Table 2: High-Risk Pregnancy: Drugs With Adverse Effects During Pregnancy ). Labor and delivery: Certain precautions are required to ensure an optimal outcome. Timing of delivery depends on fetal well-being. Women are told to count fetal movements during a 60-min period daily (fetal kick count) and to report any sudden decreases to the obstetrician immediately. Nonstress testing (see Normal Pregnancy, Labor, and Delivery: Fetal Monitoring) is begun at 32 wk and, if

results are nonreassuring, is followed by a biophysical profile (measurement of amniotic fluid and fetal muscle tone, movement, and breathing pattern). These tests and similar noninvasive prenatal fetal monitoring tests (called antenatal testing) are initiated earlier if women have severe hypertension or a renal disorder or if fetal growth restriction is suspected. Amniocentesis to assess fetal lung maturity is often necessary in women with the following:

Obstetric complications in past pregnancies Elective delivery before 39 wk Inadequate prenatal care Uncertain delivery date Poor glucose control

Type of delivery is usually spontaneous vaginal delivery at term. If labor does not begin spontaneously by 38 to 40 wk, induction is necessary because of the increasing risk of stillbirth and shoulder dystocia. Dysfunctional labor, fetopelvic disproportion, or risk of shoulder dystocia may make cesarean delivery necessary. Plasma glucose levels are best controlled during labor and delivery by a continuous low-dose insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph infusion. If induction is planned, women eat their usual diet the day before and take their usual insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph dose. On the morning of labor induction, breakfast and insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph are withheld, baseline fasting plasma glucose is measured, and an IV infusion of 5% dextrose in 0.45% saline solution is started at 125 mL/h, using an infusion pump. Initial insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph infusion rate is determined by capillary glucose level. Insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph dose is determined as followed:

Initially: 0 units for a capillary level of < 80 mg/dL (< 4.4 mmol/L) or 0.5 units/h for a level of 80 to 100 mg/dL (4.4 to 5.5 mmol/L) Thereafter: Increased by 0.5 units/h for each 40-mg/dL (2.2-mmol/L) increase in glucose level over 100 mg/dL up to 2.5 units/h for levels > 220 mg/dL (> 12.2 mmol/L) Every hour during labor: Measurement of glucose level at bedside and adjustment of dose to keep the level at 70 to 120 mg/dL (3.8 to 6.6 mmol/L) If the glucose level is significantly elevated: Possibly additional bolus doses

For spontaneous labor, the procedure is the same, except that if intermediateacting insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph was taken in the previous 12 h, the insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph dose is decreased. For women who have fever, infection, or other complications and for obese women who have type 2 and have required > 100 units of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph /day before pregnancy, the insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph dose is increased. Postpartum: After delivery, loss of the placenta, which synthesizes large amounts of insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph antagonist hormones throughout pregnancy, decreases the insulin requirement immediately. Thus, women with gestational diabetes and many of those with type 2 require no insulin Some Trade Names HUMULIN NOVOLIN Click for Drug Monograph postpartum. For women with type 1, insulin requirements decrease dramatically

but then gradually increase after about 72 h. During the first 6 wk postpartum, the goal is tight glucose control. Glucose levels are checked before meals and at bedtime. Breastfeeding is not contraindicated but may result in hypoglycemia if oral hypoglycemics are taken. Women who have had gestational diabetes should have a 2-h oral glucose tolerance test with 75 g of glucose at 6 to 12 wk postpartum to determine whether diabetes has resolved. Last full review/revision December 2008 by Sean C. Blackwell, MD Content last modified December 2008

Progression of retinopathy during pregnancy in type 1 diabetes mellitus.Rahman W, Rahman FZ, Yassin S, Al-Suleiman SA, Rahman J. University Hospitals of Leicester, Leicester, UK. PURPOSE: The incidence and risk factors for progression of retinopathy during pregnancy in women with type 1 diabetes mellitus were retrospectively evaluated. METHODS: Fifty-four insulin-dependent diabetic patients at a teaching hospital in Saudi Arabia were followed throughout the pregnancy/puerperium with serial ophthalmic examination. Dilated fundus examination was performed in each trimester and puerperium. RESULTS: Progression of diabetic retinopathy in the study occurred in 13/54 (24%) patients--2/22 (9.1%) patients had no diabetic retinopathy initially, 4/20 (20%) had non-proliferative diabetic retinopathy (NPDR) and 7/12 (58.3%) had proliferative diabetic retinopathy (PDR). Of the eight patients with PDR who had no laser treatment before pregnancy, six (75%) showed progression but only one of the four patients who had PDR and laser treatment prior to pregnancy experienced progression of retinopathy. Eight patients in total received panretinal photocoagulation to arrest the progression of retinal disease during pregnancy and only one of them had laser treatment prior to pregnancy. CONCLUSION: Laser photocoagulation for severe NPDR or early PDR prior to pregnancy may protect against rapid progression of PDR. Visual impairment resulting from progression of PDR can be prevented by aggressive laser treatment during pregnancy. Duration of diabetes>15 years, poor glycaemic control and hypertension are high-risk factors in the progression of diabetic retinopathy in pregnancy. PMID: 17430509 [PubMed - indexed for MEDLINE]

MeSH Termshttp://www.pakmedinet.com/4704

Chapter 36

Pregnancy in Preexisting DiabetesThomas A. Buchanan, M.D.SUMMARY

D

ata from birth certificates in the United

States indicate that maternal diabetes complicates 2%-3% of all pregnancies, but these data may underestimate the true prevalence of maternal diabetes in pregnancy. Two major forms of maternal diabetes may occur during pregnancy: preexisting or "pregestational" diabetes, and gestational-onset or gestational diabetes mellitus (GDM). Only the former is known prior to pregnancy, and this form constitutes ~10% of cases of maternal diabetes. Thus, prevalence rates for pregestational diabetes appear to be in the range of 0.1%-0.3% of all pregnancies. These pregnancies are at risk for both maternal and fetal complications. Fetal complications of maternal diabetes can be divided into two major categories. Complications that arise from the effects of maternal diabetes on early fetal development (i.e., in the first trimester) include spontaneous abortions and major congenital malformations. In the absence of special preconceptional diabetes management, spontaneous abortions occur in 7%-17% of diabetic pregnancies and major malformations occur in 7%-13%. Rates of both complications are highest in women with the most marked hyperglycemia during the first trimester, and the rates of malformations appear to be decreasing in countries and medical centers where standards of diabetes care result in improved maternal blood glucose control prior to and during early pregnancy. The most prominent

fetal complications that can arise during the second and third trimesters are stillbirth and macrosomia (an excessively large infant). Stillbirths are now uncommon in diabetic pregnancies; congenital malformations and complications of maternal hypertensive disorders account for most of the 1.5- to 2-fold increase in perinatal mortality compared with nondiabetic pregnancies. Macrosomia appears to be the most frequent fetal complication, affecting 10%33% of infants, depending on the definition used for macrosomia. Macrosomia increases the risk of birth trauma and has been associated with a long-term risk of obesity in offspring. Maternal risks in diabetic pregnancies are greatest in the presence of preexisting microvascular disease (retinopathy and nephropathy). Diabetic retinopathy is present in 15%-66% of women early in pregnancy, and the retinopathy frequently worsens during gestation, especially when severe background or proliferative changes are present early on. Laser photocoagulation therapy prior to pregnancy can reduce the risk that proliferative retinopathy will worsen during gestation. Overt diabetic nephropathy is present before pregnancy in 5%-10% of patients; of these, two-thirds manifest hypertensive disorders during gestation. The hypertensive disorders precede pregnancy in approximately half of the cases and develop during pregnancy in the other half. Overt diabetic nephropathy in mothers increases the prevalence of intrauterine growth retardation and prematurity in infants; fetal morbidity and mortality increase as well. The long-term impact of pregnancy on diabetic retinopathy and nephropathy in mothers is not known.

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There is no national surveillance program for diabetes during pregnancy in the United States. As a result, it is not possible to determine true national prevalence rates for diabetes during pregnancy or for the various maternal and fetal complications that can occur when diabetes and pregnancy coexist. Data to help estimate prevalence rates for diabetes and its complications during pregnancy come from several sources. Since 1989, birth certificates in most states and the District of Columbia have included information on a variety of maternal and infant risk factors, including diabetes1. The birth certificate data provide the first national estimates of the prevalence of diabetes during pregnancy. However, the certificates do not distinguish between the focus of this chapter, diabetes that existed prior to pregnancypregestational diabetes, including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM)

and diabetes that is first detected during pregnancy (GDM, discussed in Chapter 35). Birth certificate data may also suffer from inaccurate reporting of maternal and fetal complications (e.g., only 65% of maternal diabetes was recorded on birth certificates surveyed in Tennessee in 1989)2. Other data sources include regional or statewide data derived from a combination of birth certificate and hospital record information and published reports from individual medical centers. The former source may be the most complete for a specific region, although t