An interview with Dr P V Rao  in www.endocrineindia.com  July 2001
 
Dr. P.V.Rao Dr P V Rao is currently, Professor and Head, Department of Endocrinology and Metabolism, at the Nizam's Institute of Medical Sciences, Hyderabad. Dr Rao has completed M.B., B.S. from Andhra Medical College, Visakhapatanam and M.D. (Medicine) from Stanley Medical College, Madras. He has taken a Diploma in Diabetology from Institute of Diabetes, Endocrinology and Metabolic diseases, Zagreb, Croatia and has also completed Doctorate (Ph.D.) from All India Institute of Medical Sciences, New Delhi.

Dr Rao has worked in several national as well as international Medical institutions of repute, and has over 20 years of Clinical and Research experience. Dr Rao is the Secretary of RSSDI from 1994; Secretary, Accreditation Committee for Post-graduate programs in Diabetology since 1995. Besides he is also the Founder Secretary of Andhra Pradesh Diabetic Federation (1992) and Founder Secretary of Diabetic Self-Care foundation (1993).

Dr P V Rao has presented several research papers at various national and international medical conferences and has to his credit more than thirty publications in national and international journals.

Dr P V Rao brings you the answers to the questions on "Gestational Diabetes":

Q1. What guidelines would you recommend which may help a woman in the management of gestational diabetes in various stages of pregnancy?

Ans. A specialist team including a physician and an obstetrician should see all pregnant diabetic women in a combined clinic, in a hospital with a neonatal intensive care unit.

Pre-Pregnancy Care:

All diabetic women should receive advice from someone understanding their individual contraceptive and pre-pregnancy needs:

    to assess suitability for pregnancy,
    to optimize control in very early pregnancy, and
    to give information about pregnancy and general measures to improve outcome.
Management of Diabetes:
    Diet
    Diet plus insulin if pre-meal venous plasma glucose is 100 mg/dL or above
Management of Pregnancy:

All diabetic pregnant women should have:

    Tight control of diabetes during pregnancy to reduce complications of pregnancy and reduce the mortality and morbidity of the infant.
    Education about the treatment of hypoglycaemia and avoidance of ketoacidosis.
    24-hour access to the specialist team.
    Access to dietitian and nurse in the antenatal clinic.
    Quality ultrasound scanning to assess gestation and fetal growth and to look for abnormalities.
    Fetal monitoring, particularly if at very high risk.
    Regular examination of fundi and assessment of renal function.
Delivery:
    Women with good diabetic control and no complications of diabetes or pregnancy may be delivered at 39-40 weeks. Those at high risk should be delivered earlier.
    During labour or Caesarean section blood glucose should be normalized using intravenous glucose and insulin supervised by the specialist team.
    An experienced paediatrician should be available.
    Breast feeding should be encouraged.
Q2. What are the recent advances in the management of gestational diabetes?
 

Ans. Gestational diabetes mellitus was defined as "carbohydrate intolerance of variable severity, with onset or first recognition during pregnancy." Controversy continues to surround every aspect of this clinical entity known as gestational diabetes. There is no consensus regarding diagnostic criteria, the utility of universal screening, or the association of gestational diabetes with perinatal morbidity and mortality. Gestational diabetes may still be a "a non-entity" whose only clinical association is with an increased maternal risk of subsequent diabetes.

WHO classified all pregnant women with diabetes mellitus or IGT as having gestational diabetes, not confining to diabetes detected during pregnancy alone.

Prior studies have suggested that macrosomia is the only morbid condition associated with gestational diabetes and that this association is the result of confounding by maternal obesity rather than a result of gestational diabetes itself.

The cause of fetal macrosomia associated with gestational diabetes is yet another subject of current controversy. Classically, the Pedersen hypothesis based macrosomia in fetal hyperinsulinemia, is a consequence of maternal hyperglycemia. Later studies supported this hypothesis in that insulin therapy to normalize maternal blood glucose levels was found to reduce the frequency of macrosomia compared with results with routine prenatal care or treatment with diet therapy alone.

Numerous studies that followed also reported decreased rates of macrosomia, cesarean section, and neonatal complications with vigorous efforts to optimize maternal glycemic control with Insulin

Q3. What therapy would you recommend for optimal management of gestational diabetes?

Ans. As soon as possible after diagnosis, all patients with gestational diabetes are instructed by a dietitian in an individualized diet based on basal requirements calculated using pre-pregnancy weight and an activity allotment, plus 300 calories per day to account for pregnancy requirements.

The daily calorie allotment is divided among three meals and an evening snack, with approximately 60% in the form of carbohydrate, 20% protein, and 20% fat.

Blood glucose monitoring is initiated 1 week after the start of dietary therapy and consists of weekly fasting and 2-hour post-breakfast plasma glucose determinations.

If fasting or 2-hour post-prandial plasma values equal or exceed 100 mg/dl or 126 mg/dl, respectively, insulin therapy and weekly ( daily in a few cases ) self-monitoring of blood glucose values are initiated.

The majority of patients with gestational diabetes requiring insulin are treated with a twice daily injections of intermediate-acting insulin (usually 10 units NPH insulin before breakfast and dinner) and twice-daily blood glucose monitoring (generally fasting and before the evening meal).

The remainder are treated with a split-mixed regimen consisting of one to two injections of NPH insulin plus regular insulin and blood glucose monitoring three to four times daily.

Insulin doses are increased in 5-unit increments until blood glucose levels are within the goal range. Venous plasma glucose goals are <100 mg/dL fasting and before meals or =<125 mg/dL 2 hours post-prandially.

Q4.  What is the effect of maternal gestational diabetes on the foetus?

Ans. Hyperinsulinemia in the fetus of the diabetic mother increases fetal metabolic rate and oxygen requirements in the presence of several factors, such as hyperglycemia, ketoacidosis, pre-eclampsia, and vascular disease, which reduce uteroplacental blood flow and fetal oxygenation.

Chronic fetal hypoxia is exacerbated further in poorly controlled patients, in whom a shift to the left in the maternal oxyhemoglobin dissociation curve results in increasing hemoglobin affinity and, therefore, reduces red cell oxygen delivery at the tissue level.

Extramedullary hematopoiesis is frequently observed in stillborn infants of the diabetic mother (IDM) signifying that chronic intrauterine hypoxia is the likely cause of these losses. Intrauterine fetal cord blood sampling of diabetic pregnancies have demonstrated the association of maternal diabetes with polycythemia and associated acidemia.

Reduced uterine blood flow, and thereby diminished oxygen and substrate delivery, is an etiologic factor in fetal growth retardation observed in women with diabetic vascular disease.

In ketoacidosis, hypovolemia and hypotension may reduce intervillous blood flow, whereas in pre-eclampsia, narrowing and vasospasm of spiral arterioles may result. Other placental lesions common in diabetic pregnancies, such as villous immaturity, premature senescence due to hypoxic damage and repair may also impair intervillous exchange.

The perinatal complication most frequently associated with gestational diabetes is fetal macrosomia, which is associated with increased rates of secondary complications such as operative delivery, shoulder dystocia, and birth trauma such as brachial plexus injury, nerve palsy, or bone fracture.

Neonatally, children born of diabetic mothers may have hypoglycemia with plasma glucose level <40 mg/dl; hypocalcemia as total serum calcium level <7 mg/dl or ionized calcium level <4.5 mg/dl; polycythemia as central hematocrit value of >65%; hyperbilirubinemia as indirect bilirubin level exceeding expected norms for gestational and postnatal age that necessitates phototherapy; and RDS as ground glass appearance on chest x-ray film combined with pediatrician's judgment of a clinical course consistent with RDS.

Q5. Besides blood glucose monitoring which special laboratory investigations would you recommend in a patient with gestational diabetes?

Ans.  Non stress Test, Contraction Stress Test, and Fetal Biophysical Profile by Ultrasound, permit evaluation of fetal breathing movements, gross body movements, fetal tone, and amniotic fluid volume, and detect major fetal malformations in patients who have not been studied earlier in pregnancy.

Maternal evaluation of fetal movements has proven to be a simple and inexpensive yet valuable screening technique to assess fetal condition in high-risk pregnancies.

Doppler velocimetry has been proposed as a clinical tool for antepartum fetal surveillance in pregnancies at risk for placental vascular disease. Because women with insulin-dependent diabetes are at increased risk for pre-eclampsia and fetal growth retardation.

The value of the lecithin/sphingomyelin (L/S) ratio has been questioned in pregnancies complicated by diabetes mellitus. The presence of the acidic phospholipid phosphatidylglycerol (PG) is the final marker of fetal pulmonary maturation. The obstetrician should be aware of neonatal outcomes at his or her institution at various L/S ratios in the presence or absence of PG.

Q6. Which is the most economical method for routine screening of gestational diabetes?

Ans.

    Test urine (preferably fasting) for glucose at every visit.
    Test plasma glucose if 1+ or more glycosuria,At first visit and at 28 weeks:
    If plasma glucose is =100 mg/dL at 2 hrs from food, or
                                   =126 mg/dL at less than 2 hrs from food then carry out 75 g OGTT.
Criteria for diagnosis:

75 g OGTT: =100 mg/dL in fasting or
                  =140 mg/dL at 2 hours after OGTT.

Q7. How effective and safe are oral anti-diabetics in gestational diabetes?

Ans. Sulfonylurea drugs such as tolbutamide and chlorpropamide induced profound hyperinsulinemic hypoglycemia among neonates born to women who took these drugs during pregnancy. The combination of transplacental passage of a sulfonylurea drug and glucose which itself is the most powerful secretagogue would stimulate even more fetal insulin production, further stimulating fetal growth (macrosomia). The causes of late fetal deaths in pregnancies were due to fetal hypoxemia directly resulting from hyperinsulinemia induced by sulfonylureas. Hyperinsulinemia stimulated increased extraction of oxygen from fetal blood by the fetus, beyond the ability of the placenta to supply it, and resulted in fetal hypoxemia.Studies in animals demonstrated that sulfonylurea drugs had teratogenic and toxic effects on the fetus. Retrospective studies of series of women with type 2 diabetes mellitus suggested an association between first-trimester sulfonylurea therapy and major congenital malformations. Women treated with metformin had increased prevalence of pre-eclampsia and perinatal mortality in the third trimester.

However, a few authors continue to defy conventional wisdom and propose an alternative treatment for women with gestational diabetes.

Q8.  Do you see any role of insulin delivery systems in gestational diabetes?

Ans. Insulin pen syringe devices have greatly facilitated intensive management protocols with multiple insulin injections in a single day, often with two different types of insulin.

Insulin pumps are cumbersome, and are not generally used in India for management of diabetes during pregnancy. But better insulin preparations with least clogging and without the necessity of changing the needles too often, may favor more use of pumps in near future.

While currently available insulin syringe pump devices are suited for subcutaneous insulin injections, as more and more diabetic women are given glucose and insulin infusions during delivery, insulin pumps may also have a role in intravenous insulin delivery protocols.
 

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