The Severity of Diabetes in Pregnancy

The Severity of Diabetes in Pregnancy

THE SEVERITY OF DIABETES IN PREGNANCY WAL'l'ER S. ,JONES, M.D., PROVIDENCE, R. I. (From the Providence Lying-In Hospital) T ilE ir~creasing nu...

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THE SEVERITY OF DIABETES IN PREGNANCY WAL'l'ER

S.

,JONES,

M.D.,

PROVIDENCE,

R. I.

(From the Providence Lying-In Hospital)

T

ilE ir~creasing numbe1: of .diabetic .patients a!)pearing. in obs~etrical clinies has stimulated a growmg mterest m the subJect of drabetes m pregnaw·y. It is generally agreed that the incidence of complications and the fetal sa.lvagt' IH~m· a direct relationship to the severity of the diabetes; but unhappily the I'<:' is no general agreement on what constitutes ":;;everity'' and how it is to lw elassified. There are two diametrically opposed schools of thought. \ l) that severity should be based on longevity of the disease and on progression of vascular damage; (2) that the clinical status of the patirnt, in terms of the insulin requirement, is the best yardstick of severity. ·white and her co-workers1 • 2 • a advocate what might be called the historical classification. Severity is graded on the basis of age at onset and duration of the diabetes, and on such objective findings as retinitis, vascular selerosis. and renal damage. They pay no attention to insulin requirements. Pedowitz,' on the basis of an experience >vith 1G6 viable pr<'gnancies, eoncurs in this concept. 'l'he White classification, which has received virtually semioffieial t'f'eog~ nition from this .JouRNAL, 5 is as follows:

Class A..-" Glucose tolerance test diabetes" nr "dH•mica] dia lH•t es, '· n•quiring no insulin. Class B.--Onset oVCJ' age 20; tlnration less than 10 years; 110 vascular disease. Class C.-Onset age 10-19; duration 10-19 years; minimal vascular damage. Class D.-Onset under age 10; duration ove1· 20 .nars; hypertrnsion. r·otinitis, or minimal vascular selerosis. Class E.-Calcified pelvic vessels. Class P.-Nephritis. Oecupying a neutral position on the subject, Oakley 6 found no (•ot'I'elation between either age at onset or duration of disease, in a series of 267 English cases. Similarly Hnrwitz, 7 with 124 cases, reports a lower fetal loss in mothers requiring no insulin or in those whose diabetes was unmasked during tlH' pregnancy, as comparrd with that in patients requiring insulin or thosr whose •lisease antedated the gestation. lie concludes, "however, beyond this then· appears to be no statistical Jifferenee in fetal mortality between pati0nts with mild and those with severe diabetes, or· between those with cases of short alll1 those of long duration.'' The leading advocates of the opposite point of view are 'l'olstoi. (tiven. and Douglas, 8 • 9 who consider the metabolic statns of the patient, as expressed by tho insulin requirement, to be the paramount criterion of severity. They believe that the woman, even without long duration or vascular damage, who 3JS

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SEVERT'rY OF IlTABETER IN PREGNAKCY

31!)

is prone to ketosis and who requires large amounts of insulin to remain in control, has severe diabetes. They feel that those who are "influenced by the degTee and extent of vascular disease ... have been measuring the concomitants or sequelae of diabetes and not severity as judged by difficulty in management.'' In general we have leaned to this latter viewpoint. In 1953 we10 published the twenty-five-year experience with diabetes at the Providence Lying-In Hospital. In classifying the severity of our cases, we tended to follow the diag·nosis of the internists concerned. This was usually predicated on the insulin requirement, with due consideration given to such factors as vascular and renal changes, and the "brittleness" of the diabetes. When we attempted to break down our cases into the White system of classification, we found that a substantial proportion of what we considered to be severe diabetics fell into White's relatively mild Class C. These patients exhibited a disproportionately high incidence of complications and fetal loss. Conversely, many of the cases which, because of essential hypertension, fell into the more severe White Class D, w<:>re clinically so mild as to require little or no insulin; and these contributed a minimum of complications and fetal loss. In our experience the White system of grading severity on a historical and vascular-damage basis alone is not entirely satisfactory. 11 All this confusion of evidence has intrigued us into a study of the problem. In order to be consistent, White's standard of viability (960 grams), her historical-vascular classification of severity, and the Joslin Clinic level of insulin "severity" will be used. The objectives are to attempt to evaluate: (a) what, if any, correlation there may be between the clinical severity, expressed in insulin requirement, and the physiological-obstetrical complications of pregnancy; (b) the relative importance of the insulin demand, as compared to the historical progression of the disease, in the determination of the severity of the diabetes. Material The material here presented comprises 204 viable pregnancies delivered at the Providence I.~ying-In Hospital in the twenty-eight-year period 1927-19fi4 (Table I.) TABLE

I.

DIABETES IN PREGNANCY,

1927-1954 121,927

Total deliveries in the hospital Total pregnancies in diabetic patients Cases not included in statistics: Delivered elsewhere, etc. Nonviable (under 960 grams) Cases used for this stu.dy: Hormone treated Non-hormone treated

219 :l

12 15

15

21

183 204

204

Of these 204 patients, 21 received hormone therapy anu 183 did not. Table II demonstrates that the results, with the exception of the section rate, are so comparable that both groups may be pooled as a single series for the

320

Afll .. L Ob~t. & Gywz-t

.JONES TABLE

II.

cases) Hormone Therapy (21 eases) 'rotal series

february,

19~(,

OBSTETRICAl, COMPLICATJOKS, HORJI1ot;~; VS. NOX·HOR~IONE THERAPY

8

38.1

(j

28.t}:!;

t)/

( 204 cases '1

:JS.6

](j

7tL2

~6.5

ii-t

8f) ..j

ti

:28.6

:J8.0

------~-··--·------~~~----------~"···~--

.Applies to pre-eclampsia and superimpo~ed pre-eclampsia in all charts and tables. Does not include 17 cases of uncomplicated essential hyper-tension. tFetal loss in all charts and tables refer~ to uncorrected gross stillbirth and neonatal loss of infants weighing over 960 grams. +This does not prove that stilbestrol prevents toxemia. Each case in the small group has a value of 5 per cent; one more patient would bring the figure above that of the nonhormone series.

purpose of this study. \V e are not uow debating the merits of hormone versus non-hormone management, nor the question of resarean section in diabetes. Our only comment on this chart is that we are not convinced that the results justify increasing the section rate to 76 per cent in the hormone group. Granting that two-thirds of these rases were severe diabetes by any standard, review of the records suggests that (in our personal opinion) a rate of about 48 per cent would have bc>rn appropriatr in this particular group of wom('ll. Distribution by White 1s Classification of Severity.

60

Fig. 1.

The series is distributed according to the White classification of severity in Fig. J. It will be seen that two-thirds fall into the mild Classes A and B, while only one-third are in the more severe categories C and D. Although we had several patients suspected of renal damage, none of them could definitely be placed in Classes E or F. Of the women who had pelvic x-rays, none showed calcification of vessels. This large number of relatively mild cases is attributable to two influences: ( 1) It is the type of spread commonly reported by obstetrical services, as distinguished from diabetic clinics. (2) The series goes back into the era when very few young diabetic patients or those with severe cases survived into the childbearing age. Until ten years ag·o the usual patient was the oldet' woman with a rather mild case who was also frequently a multipara. It is only in recent years that we have begun to harvest the crop of primiparous, severely affected, juvenile diabetic patients.

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Insulin Requirement It has been our clinical impression that, although a few comparatively mild cases of diabetes seem to become ''brittle'' under the stress of pregnancy, most of the patients who give serious difficulty in control are those whose normal nonpregnancy insulin requirement is high. This aroused our interest in the comparative behavior of women with low and with high insulin demands. The Joslin Clinic 2 classifies medical diabetes as follows, depending somewhat on the carbohydrate intake: .ilfild.-Sugar free on 150 Gm. carbohydrate, without insulin. Moderately Severe.-Sugar free on 150 Gm. carbohydrate and 10 units insulin; or more carbohydrate and 20-50 units of insulin. Severe.-Requires over 50 units of insulin on 150 Gm. carbohydrate. Since the pregnant woman usually consumes 150 Gm. or more of carbohydrate, 50 units is an appropriate standard of severity for this study. In the actual practice of our own clinic, the internists frequently label a case as severe at the 40 unit level of demand; and Given and associates 8 mention that half their patients required 40 to 60 units a day, possibly implying that they regard 40 units as approaching the severe clinical range. If the data which follow were computed on the basis of 40 units as the critical level of severity, the curves shown would be more striking. In order to be objective, however, this study is based on the 50 unit medically severe standard used by White's clinic. Furthermore, this is the normal non pregnancy requirement, or that at the outset of gestation; not the peak incr-ease attained during pregnancy. Oakley 5 states that "there is no significant difference between the fetal mortality in non-insulin-treated and insulin-treated diabetic mothers"; and fiiven and eo-workers 8 report a fetal loss of 22.6 per cent in patients not requiring insulin, as compared to 2fi.6 per cent in the women who used insulin. At first glance our results would appear to substantiate this, as the gross fetal loss was 28.2 per cent in insulin cases, and 27.3 per cent in nontreat.ed women. The latter figure, however, includes 8 fetal deaths in patients who were acidotic when the disease was first discovered, or in acidosis du<' to gross negligence on the part of themselves or their physicians. If these preventahle losses are cort·ected for, the fetal mortality in the women who dicl not need insulin was 14.9 per c·c'nt, or half that of the insulin-treated cases. TABLE

I

III.

GJIAMIER 1:\ lNRULIK RF;QVIRE~H;:\'T

NO. OF INSULINTREATED CASES

Increased requirement No significant change Diminished requiremest T~~-

98 40 14

I

PER CENT ALT, INSULIN CASES

I

FETAL LOSS

REQUIREMENT OF 45 1 'INSULIN SEVERE'' DIABETIC PATIEN'l'S

27.5% 21.4%

6/45-13.3% 1/4fi- 2.2%

64.5;--~--'-~;;::29::-.4-:co/t::;-0~-'---;;:3;:;-8/-;-;4:;;5--;8;-;4-;;.5:-;:o/t;-o-

26.3 9.2

152______ioo--::.o-----,2c-::s-;:;.3::::%;-----------'---

Note.-(1) The fetal loss increases slightly as the insulin .demand increases.

(2) The "insulin-severe" diabetic patients exhibited an increased insulin requirement out of proportion to that of the insulin patients as a group.

It is recognized that the insulin requirement of some women increases, while that of others diminishes during pregnancy; but the statistics concerning these shifts vary widely in different reports. Our experience is recorded in Table III. Of the 152 patients who were on, or had recently been on, insulin at the outset of pregnancy: 64.5 per cent required more insulin; 26.3 per cent

.TONEf:l

322

Arn.

J. Ol»t.

& Gynec.

Fl:'bPLHV, lq~()

showed. insignificant fluctuations in either direction; and 9.2 per cent showed a definitely diminished requirement. Study of this table brings out two interN.;ting points: (1) Although the figures are not very striking, the fetal loss follows the trend of the insulin demand, going up somewhat as the r<'qnir·enwnt increases. (2) The shift in requirement in the insulin-severe cases >vns out of proportion, as compared to the diabetic patients as a group. Of the 4-il wom('ll with an initial level of 50 units or more, 84.5 per cent inerrased their dr·mnnds; and only one (2.2 per cent) had a diminished demaw1. These arr twn of thr• fragments of information which lead us tu ennsider the normal insulin requirement of the patient to be a matter of importance in evaluating diabetes in ])l'!''f£nancy, and cause us to regard the insulin-Revere case with a jaundiced ~'Y•'· Acidosis

Interest in the insulin level naturally revolves around the problem of keeping the case in control. This is particularly vital in pregnancy. :::.:e,·eral writers have emphasized the harmful effect on the fetus of 1even mild dPgreps of ketosis; and frank acidosis in our experience is by far the greatest single contributor to fetal ckath. It is, howev0r. not very informative simply tn tabulate the episodes of acidosis in pregl!fuwy. It is important to understand some of the causes for break in conh·ol, and in what kintl of womnn thf'y o<·cur. Table IV demonstrates that. 61 per eent of 1hP achlosis wr' encounterPd shonld have been preventablP, anu that this wa~ :tt;SOCiated with OVt'l' one-third of tlli' g·ross fetal loss in the series. By grad0s of sPverity. GO per eent of the aeidosis in Class B, 37 per cent in Class C, and 36 p<•J· cent in Class D was preventable: and, furthermore, 73 peP c<>nt of this prevrntahle a1·i•losis oeeuned in the "illsulin-mild" patients. In other words, mof.ii of the trouble was with the wnm!'JI who should do the best; and it was too ol'i€'11 the res11lt of ear<>les~m'HS on the part of patient or physician. TABLE

lV.

A<'lUOSIS,* CAUSES A:-iD F'ET,\L

Los::;

PF.R CE:
f'AHES

1. l:ncooperative patient 2. Inadequate medical supervision 3. Undiagnosed until in acidosiR 4. Intercurrent infection G. ''Brittle'' diabetes under compe· t.ent medical

17

11

i)

\Ul

l:l

::4.0

;.;

l·Ul

60.0

:w.s ::7.;)

54 *The preventable acidosis in categories 1, 2. and 3 represents 61.~ per cent of all aci'L". and is associated with 38.6 per cent of the gross fetal loss in diabetes.

When this preventable element in the acidosis picture is correded fu1', what might be expected is found: There is substantially more acidosis due to such :factors as "brittle" diabetes and intercnrre11t in:feetion in the patient::; whose insulin requirement is 50 or more units a day. Obstetrical Complications

In addition to acidosis, two other physiological eornplications peeuliar to pregnancy are evidently detrimental to the welfare of the fetus: pre-eclampsia, ~lone or superimposed on essential hypertension, and hydramnios. Singly or m combination, these three contribute to the great majority of perinatal fetal deaths.

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l<'ig. 2 graphs these components, for insulin-mild and insulin-severe cases, in each of the White classes of severity :

Toxernia.-No correlation would be expected between insulin demand and the appearance of pre-eclampsia, and none exists. Half of the sharp rise in the insulin-severe cases in Class D is due to pre-eclampsia superimposed on the hypertension characteristic of that class. Hydramnios.-This condition is a frequent concomitant of both toxemia and acidosis, and the incidence is consistently higher in insulin-severe diabetes. Aciclosis.-As previously mentioned, when preventable cases are corrected out, acidosis is more frequent in the insulin-severe case. Except in Class C, where both the gross and the corrected incidence is higher in the mild category. This may in part be accounted for by the fact that Class C contains the bulk of the unpredictable ten-year juvE'nile diabetic patients.

----ACIDOSIS

40

30 20

:w

Jl'tdte Cla.uitioation ________ ... "'IMuliJMlilJ1• : Inaulln

- - - - "lrutullflooooaen:.t'e•

t

requ1r~

R~

\U'Il6t' SO unite.

SO 1U\it111

or

.aN da.s:q.

Fig. 2.

Another interesting finding is that there is less acidosis in the insulin-mild cases of Class D than among similar mild cases in Class C. Almost 60 per cent of these Class D women, despite their essential hypertension, had cases clinically so mild as to require from no insulin to less than 20 units. Although assigned a high severity rating because of their vascular disease, this group are not likely candidates for acidosis. In these relatively mild cases in older women the hypertension is the result of the normal aging process, and has little or nothing to do with either the duration or the severity of the diabetes.

Am. J. Ob,t. & Gynec. Feoruarv. l'l56

JONES

324

Thus the hypertension in these eases ser\"l'S only as a t·(·ll herring. to eonfust• the results in the severity classification. This i:-< certainly one of the tlefrets of the White system. Fetal Loss.-The gross fetal loss is higher i11 insulin-severe diabetes; except in Class 0, where the peaks of pre-eclampsia and uncorrected acidosis coincide to produce a greater fetal wastage in the mild category. Fig. 3 summarizes the findings; ·while the insulin-sev<"re cases cornprise only one-fifth of the diabetic series, they eontrilmte more than their proportionate share of complications and of the resultaut fptalloss.

90

eo 70 60

so

43.1.%

w..s%

110 .)()

20 lO

Cll:nically •atld• s IMulin r.qld.n•nt under $0 un1U.

Cl1.nicall.r MeeVRe" : Requin~~ent SO units and mtll"tt a d•f•

Fig. :J.

Evaluation of Results In an attempt to evaluate these data, it must be remembered that although this is a sizable collection, as diabetes reports go today, the volume of material is actually small for statistical purposes. It provides an impression rather than proves anything concrete. In Fig. 2, the uphill climb of the curves across the field from A to D is reasonably consistent. This tends to uphold the validity of the historical-vascular concept of classification. Less consistent are the differences in level of the insulin-milu and the insulin-severe curves in Fig. 2; and less significant is the relative space occupied by ''severe'' in the more important blocks (acidosis and fetal loss) in l<'ig. ;~. From this one may surmise that: (A) There is a correlation between clinical severity, expressed in insulin demand, and the complications and fetal loss in pregnancy. (B) Insulin demand, however, appears to be less important than the historical and vascular progression of the disease in determining the severity of the diabetes.

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Classification 'fhe White classification has been a major contribution to the thinking in the field of obstetrical diabetes. It is basically sound; but in its present form it is too cumbersome, and certain technical difficulties in its application have been pointed out above. When employed in a study such as this it presents an immediate stumbling block: only a very large series is susceptible to being divided six ways, without ruining the statistical validity of the smaller components. If it is further subdivided (insulin mild and severe) into twelfths, confusion is compounded. It should be possible to arrive at a more compact and workable classification. This might conveniently consist of four major historical-vascular classes of the White type, which could then be subdivided into insulin-mild and insulin-severe, for a total of not more than eight groups.

Conclusions Two hundred four viable pregnancies in diabetic women are reviewed in an effort to ascertain what, if any, correlation may exist between: (a) the historical and vascular encroachments of the disease process; (b) the clinical severity as expressed by insulin requirement; and (c) the obstetrical complications and fetal loss. The information obtained suggests that: I. The concept that age of onset, duration, and evidence of vascular uamage are criteria of severity in diabetes is a sound one. It should probably remain basic in any classification. 2. There is also a significantly higher incidence of the physiological complications peculiar to pregnancy, and of fetal loss, in those patients whose normal daily insulin requirement is high (50 units and more). 3. Both these factors should be taken into consideration in the evaluation of the severity of a case of diabetes in pregnancy; and both should be included in the formulation of a definitive classification of diabetes in pregnancy. 4. The "White classification is a good prototype, but there are certain practical objections to it in its present form. What is needed is a more simple and compact classification, <'mbodying the principles here outlined. References 1. White, P.: Am. J. Med. 7: 609, 1949. ~. Joslin, E. P., Root, H. F., White, P., and Marble, A.: The Treatment of Diabetes Mel· litus, ed. 9, Philadelphia, 1952, Lea & Febiger. 3. Nelson, H. B., Gillespie, L., and White, P.: Obst. & Gynec. 1: 219, 1953. 4. Pedowitz, P., and Shlevin, E. L.: Bull. New York Acad. Med. 28: 440, 1952. 5. Editorial. AM. J. 0BST. & GYXEC. 67: 210, 1954. 6. Oakley, W.: Brit. M. J. 1: 1413, 1953. 7. Hurwitz, D., and Higano, N.: New England J. )fed. 247: 305, 1952. 8. Given, W. P., Douglas, R. G., and Tolstoi, E.: AM. J. OBsT. & GYNEc. 59: 729, 1950. 9. Tolstoi, E., Given, W. P., and Douglas, R. G.: J. A. M. A. 153: 998, 1953. 10. Jones, W. 8.: AM. J. OBST. & GYNEC. 66: 322, 1953. 11. Nelson, H. B., and Jones, W. S.: AM. J. OBST. & GYKEC. 67: 224, 1954 (Correspondence).