1991, 34: 205-210 International Federation of Gynecology and Obstetrics

Int. J. Gynecol. Obstet.,

Noninsulin Mexico

dependent

J. Contreras-Soto,

G. Forsbach,

Hospital dc Gineco-Obstetricia (Mexico)

205

diabetes mellitus and pregnancy in

J. Vazquez-Rosales,

C. Alvarez-Garcia

“‘Dr. I. Morones’*, IMSS and Uniakd de Investigaciones

and G. Garcia

Biomedicas &I Noreste. IMSS Monterrey,

N.L.

(Received April 27th, 1989) (Revised and accepted January 2Oth, 1990)

Abstract

nal morbidity; Congenital defects.

however, close control of plasma glucose levels and adequate perinatal care have brought about a decrease in maternal morbidity and in perinatal morbidity and mortality, although these are still slightly higher than in the general population [4,7,11]. Most reports on diabetes and pregnancy have focused on insulin dependent diabetes mellitus (IDDM) while information about noninsulin dependent diabetes mellitus (NIDDM) is scarce and usually not included in discussions on pregnancy and diabetes, since this type of diabetes usually occurs in women that have already finished their reproductive activity [3,4,7,10,11,15]. However, NIDDM has shown a higher prevalence and earlier appearance in some ethnic groups, such as Pima Indians [9], Arabians [2], MexicanAmericans [8] and the Mexican population [I], while IDDM has a relatively lower prevalence in these groups. We decided to evaluate our clinical experience with diabetes and pregnancy in our population, where NIDDM represents more than 50% of our diabetic pregnant patients. We report herein 215 consecutive pregnancies with diabetes treated at the Hospital de Gineco-Obstetricia “Dr. I. Morones”, IMSS in Monterrey, Mexico.

I&OdWtiOll

Patients and methads

Diabetes mellitus in pregnancy is a well known risk to both mother and offspring;

Our population is a middle class ethnically homogeneous population. Women with pre-

0024%7292/91/$03.50 0 1991 Intemational Federation of Gynecology and Obstetrics Published and Printed in Ireland

Clinical and Clinical Research

We analyzed 215 consecutive patients with diabetes mellitus and pregnancy, I I8 (54.!3%) with noninsulin dependent diabetes mellitus (NIDDM), 90 (41.86%) with gestational diabetes mellitus (GDM) and 7 (3.26%) with insulin dependent diabetes mellitus (IDDM). NIDDM and GDM patients had no significant difference in age and body mass index. There were no maternal deaths, nor episodes of ketoacidosis. Maternal and neonatal complications occurred with a similar frequency in NIDDM and GDM. We concluded that in our population, diabetes associated with insulinresistance occurred in over 96% of our pregnant diabetic patients and was associated with an increased prevalence of maternal and neonatal complications. Earlier perinatal care has to be established in NIDDM patien ts, and obese young women should be screened to detect GDM from early gestation and advised to reduce weight before pregnancy ensues. Keywords Pregnancy; Diabetes mellitus; Mater-

206

Contreras-Sot0 et al.

existing diabetes and women with gestational diabetes mellitus (GDM), were recruited when they were referred for care to our antenatal clinic, which is a combined medical and obstetric clinic. Patients with NIDDM (n = 118), requiring hypoglycemic drugs to control glucose levels were switched to insulin therapy when they first attended the antenatal clinic. GDM was diagnosed in pregnant women when fasting glucose levels greater than 140 mg/dl were detected on at least two occasions (n = 90); these patients were initially treated with a low carbohydrate diet, but insulin therapy was instituted if fasting and 2-h glucose levels were over 100 mg/dl and 130 mg/dl. IDDM patients (n = 7) were already on insulin therapy; insulin doses were adjusted to meet the goal of treatment, which was to keep fasting and 2-h postprandial gucose levels below 100 mg/dl and 130 mg/dl, respectively, urinalysis without glucose or ketone and glycosylated hemoglobin (GHb) within the normal range after 2 months. All patients were treated as outpatients and were seen at weekly intervals. Diet therapy was designed to provide 36 Cal/kg of ideal weight distributed as follows: l/S for breakfast; 2/5 for lunch; and 2/5 for supper. Calories were fractionated to contain 20-25% as proteins, 45-500/o as carbohydrates and 30-35% as fats. All patients underwent weekly urinalysis, and fasting and 2-h postprandial blood glucose analysis. Patients who were not able to control their glucose levels after two visits were hospitalized to establish adequate insulin and diet therapy. GHb was measured at monthly intervals. Ultrasound B-mode scans were obtained at 18-22 weeks and at 3636 weeks of gestation. Nonstress tests were initiated at 32 weeks of gestation and repeated weekly until 36 weeks of gestation, and biweekly thereafter. Nonreactive nonstress tests were followed by a contraction stress test. In the presence of a positive contraction stress test, the patients underwent an amniocentesis for determination of the lecithin/sphingomyelin ratio and the presence of phosphatidyl glycerol. If the nonstress test was nonreactive and the contracInr J Gynecol

Obstet 34

tion stress test was positive, the patient was delivered. The newborns were clinically evaluated immediately after birth and were observed in the Special Care Nursery during the first 24 h. Large-for-gestational age newborns (LGA) were defined as those that exceeded by 2 standard deviations the birthweight in relation to gestational age [6]. Small-forgestational age newborns (SGA) were defined as those whose birthweight was less than 2 standard deviations in relation to gestational age. All infants initiated early feeding with 10% dextrose by 1 h of age. Neonatal hypoglycemia was defined as glucose levels below 40 mg/dl; hyperbilirubinemia was defined as an indirectly reacting bilirubin level greater than 12 mg/dl. Women with GDM were revaluated after delivery by a standard oral glucose tolerance test (OGTT) [ 161. Blood glucose levels were measured by glucose oxidase in plasma, glucose and ketone were screened in urine by reactive sticks (Laboratorios Miles de Mexico, S.A.). GHb was analyzed by calorimetry as described and the Fischer exact test, were used to assess the statistical significance of group differences. Results The main clinical characteristics of these patients are shown in Table I. Results are expressed as X f 1SD and range. We found no significant differences between NIDDM and GDM patients in age, parity or body mass index (BMI) and these two groups were compared (n = 208). IDDM patients were a very small group of patients and were excluded from comparison. Figure 1 shows the stage of gestation at which NIDDM and GDM patients attended the antenatal clinic for the first time; 56.78% of the NIDDM and 17.77% of GDM patients attended in the first half of pregnancy (< 20 weeks of gestation), while 43.22% of NIDDM and 82.23% of the GDM patients consulted for the first time in the second half of pregnancy. There were no maternal deaths; maternal complications (Table II) occurred in 52 (44.1%) of NIDDM patients and in 18 (20.0%) of GDM patients. The combined incidence of maternal

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Maternal morbidity associated with diabetes. NIDDM (n = 118)

Toxemia (%) Urinary tract infection (%) Chronic hypertension (%) Polyhydramnios (%) Hypoglycemia (%) Pulmonary tuberculosis (%)

17 (14.40) 16 (13.55) 5 (4.24) 4 (3.39) 6 (5.08) 4 (3.39)

Total

52 (44.1)

GDM (n = 90) 6 (6.66). 8 (8.88)* 3 (3.33). 1 (1.11)’ 18 (20)

NIDDM plus GDM (n = 208)

IDDM (n = 7)

23 (10.70) 24.(11.16) 8 (3.67) 5 (2.29) 6 (2.88) 4 (1.92)

1 I -

70 (33.7)

2

*Comparison between NIDDM and GDM showed no significant difference by the Fischer exact test. TaMe III.

Perinatal complications. NIDDM (%) (n = 118)

GDM (%) (n = 92)”

LGA Prematurity SGA Congenital defects Perinatal mortality Hypoglycemia Hyperbilirubinemia Respiratory distress syndrome Pyodennitis

35 7 3 6 3 6 5 5

31 (33.78)* 5 (5.43).

Total

71 (60.71)

(29.66) (5.93) (2.54) (5.08) (2.54) (5.08) (4.24) (4.24)

1 (0.86)

NIDDM plus GDM (%) (n = 210) 66 (31.43) 12 (5.71) 4 (1.90) 13 (6.19) 8 (3.81) 6 (2.86) 6 (2.86) 8 (3.81)

-

1 (0.48)

-

124 (59.05)

2

I (l.ll)* 7 (7&O)* 5 (5.43)+ 1 (1.09)’ 3 (3.26)* 53 (57.61)

1

I

’Two pairs of gemelar newborns. * Comparison with NIDDM showed a nonsignificant difference by the Fischer exact test. Table IV.

Congenital defects.

Major eongenital defects Cyanotic heart disease Neural tube defect

Mhu

NIDDM

GDM

Total

1 -

1

2

2 2

1

3

4

congenital defects

1

-

1 1

-

2 -

2

Syndactily Polydactily Intraventricular communication Cryptorchid Par defect Hypospadia Hydrocele

-

I I

Total

5

4

Int J Gynecol Obstet 34

IDDM (%) (n = 7)

Diabetes mellitus and pregnancy

TaMe V.

Perinatal mortality.

GDM

Total

1

1

1 I

1

2 2

-

2

2

I

1

5

8

NIDDM Immaturity Death in uterus at term Congenital cyanotic heart disease Neural tube defect Sudden unexpected death Total

209

3

mellitus have focused on IDDM, since this type of diabetes usually affects young individuals [14], but in our population NIDDM is frequently observed in young individuals. These patients usually receive hypoglycemic agents and attend later to the obstetric services. This series of patients reflects the high proportion of NIDDM in our population associated with obesity in young women; moreoever, GDM was also associated with obesity and after delivery, 65% of the patients with GDM tested by the OGTT, were diagnosed as NIDDM, suggesting an earlier appearance of NIDDM in our population. This figure is in contrast to a previous study using universal screening at 29-32 weeks of gestation, where re-evaluation after delivery showed an incidence of 11.53% of NIDDM [5]. However, in the present study most patients with GDM were diagnosed by fasting hyperglycemia over 140 mg/dl at earlier stages of pregnancy, which may represent a higher degree of carbohydrate intolerance. Obesity was a common characteristic in both groups. Maternal and perinatal complications were common and higher than in the general population. Polyhydramnios which has been proposed as a characteristic maternal complication of IDDM [4], occurred in only 5 patients; however, toxemia of pregnancy was the most frequent complication, suggesting that maternal morbidity may have other characteristics in NIDDM. Adequate perinatal care provides a better prognosis for the offspring of diabetic mothers [ 131; however, a higher incidence of congenital defects has persisted in IDDM and hyperglycemia has been disproved as a causal

I

agent [ 121.The incidence of congenital defects was 6.13%, significantly higher (P < 0.01) than 2.7% in the general population of this hospital. Also, the overall perinatal mortality was 3.81%, significantly higher (PC 0.01) than 1.9% in the general population of this hospital. The most common complication of the newborns, was LGA which occurred in 31.43% and was significantly elevated compared to the general population of this hospital (7.8%, P c 0.01); however, prematurity (7.62%) was not significantly elevated compared to the general population of this hospital (6.5%). On the basis of these data we conclude that NIDDM is the more frequent variant of diabetes in our pregnant patients; this type of diabetes occurs at earlier ages associated with obesity. GDM was associated with obesity and had similar maternal and perinatal complications, as well as a high incidence of NIDDM after delivery. Toxemia of pregnancy was the most frequent complication. The offspring of these patients was affected by a higher incidence of congenital defects, morbidity and perinatal mortality. In order to improve the neonatal outcome, earlier perinatal care has to be established in women with NIDDM who plan to become pregnant and obese young women should be advised to reduce weight before pregnancy ensues. References Alba RA, Ordonez RB: Program for detection and control of diabetes mellitus in the Mexican Institute of Social Security. Salud Publica Mex 12: 317, 1970. Al-Shawlaf T, Akiel A, Moghraby SAS: Gestational Clinical and Clinical Research

210

Conireras-Sot0 et al.

diabetes and impaired glucose tolerance of pregnancy in Riyadh. Br J Obstet Gynecol 95; 84, 1988. 3 Blumenthal SA, Abdul-Karim RW: Diagnosis, classification and metabolic management of diabetes in pregnancy: therapeutic impact of self-monitoring of blood glucose and of newer methods of insulin delivery. Obstet Gynecol Surv 42: 593, 1987. 4 Cousins L: Pregnancy complications among diabetic women. Review 1965-1985. Obstet Surv 42: 140, 1987. 5 Forsbach G, Contreras-Soto JJ, Fong G, Flores G, Moreno 0: Prevalence of gestational diabetes and macrosomic newborns in a Mexican population. Diabetes Care II: 235, 1968. 6 Garcia-Cazares S, Garcia R, Jimenez A, Quiroga M, Guzman A: The intrauterine development. Rev Med Inst Mex Seguro Sot 16: 95, 1977. 7 Hadden R: Diabetes in pregnancy 1985. Diabetologia 29: 1, 1986. 8 Hanis Cl, Ferrel RE, Borton SA, Aguilar L, Garza A, Tullock BR, Garcia CA, Schull WJ: Diabetes among Mexican-Americans in Starr County, Texas. Am J Epidemiol 118: 659, 1983. 9 Knowler WC, Pettit DJ, Savage RJ, Bennett PH: Diabetic incidence in Pima Indians: contributions of obesity and parental diabetes. Am J Epidemiol 113: 144, 1981. 10 Lavin JP, Lovelace DR, Miadonovi KM, Knowles HC, Bordan TP: Clinical experience with one-hundred seven diabetic pregnancies. Am J Obstet Gynecol 147: 742, 1983. 11 Lull& EG, Nelson RL, Hill LM, Melton J, O’Fallon WM, Evans AT: An analysis of diabetic pregnancies at Mayo Clinic, 195&79. Diabetes Care 539, 1984.

Int J Gynecol Obstet 34

12 Mills JL, Knoop RH, Simpson JL, Josanovic-Peterson L, Metger BE, Holmes LE, Aarons JH, Brown Z, Redd GF, Beeber FR, Van Allen M, Holzman I, Ober C, Peterson CM, Withiam MJ, Duckless A, Mueller-Heubach E, Polk BF and the National Institute of Child Health and Human Development: Diabetes in early pregnancy study: lack of relation of increased malformations rates in infants of diabetic mothers to glycemic control during organogenesis. New Engl J Med 318: 671, 1988. 13 Mills JL: Malformations in infants of diabetic mothers. Teratology 25: 385, 1982. 14 National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039, 1979. 15 Small M, Cameron A, Lunan CB, MacGuish AC: Macrosomia in pregnancy complicated by insulin dependent diabetes mellitus. Diabetes Care 10: 594, 1987. 16 Summary and Recommendations of the Second Intemational Workshop-Conference on gestational diabetes mellitus. Diabetes (Suppl) 34: 123, 1985. 17 Winterhalter KH: Determination of glycosylated hemoglobin. In: Methods in Enzymology, Vol. LXXVI (eds AR Bemardi, E Chiamone) p 732. Academic Press, New York, 1981. Address for reprints: G. Forsbach Apartado Postal 71 C.P. 64000 Monterrey N.L., Mexico