HELLER INSTITUTE OF MEDICAL RESEARCH THE SACKLER SCHOOL OF MEDICINE TEL-AVIV UNIVERSITY, TEL-AVIV DUPUYTREN'S DISEASE IN DIABETES MELLITUS MORDCHAI RAVID

YAEL DINAI

EZRA SOHAR

The etiology of Dupuytren's disease (DD) is unknown. The association of the palmar contracture with fibrotic conditions in other parts o f the body i 14 and the recent finding of chromosomal abnormaIities in the lCibrotic tissue a suggest that it is a generalized disease rather than a local condition 6. Some authors suggested an autosomal dominant inheritance 4, 9, others were less conclusive and introduced the term 'Dupuytren's diathesis' u to define an inherited tendency to develop D D which may express itself when predisposing conditions exist - - such as epilepsy, chronic pulmonary disease, liver cirrhosis or repeated trauma. The association of D D with diabetes mellitus (DM) was repeatedly been stressed s' 12. 16. D D was found more frequently in diabetic patients t h a n in matched controls 19 and D M was present in a markedly higher percentage among patients with D D than in controls of comparable age 15 17 18. H o w e v e r , these cumulative data were not considered sufficiently conclusive since in 'Joslin's Diabetes Mellitus' D D has been listed under 'conditions f o u n d coincidentally with D M ' 11. W e report here on a study of the incidence of D D in a large g r o u p of diabetic and non-diabetic patients. PATIENTS A N D METHODS 849 patients in two clinics for DM and 1,660 patients admitted during three months to five departments of medicine were examined for the presence of DD. The fasting blood glucose (FBG) was determined in all the hospital patients except in those with well documented overt DM. Those with FBG values ~- 110 mg/100 ml (Autoanalyzer, venous blood) were allocated to the non-diabetic group, those with FBG of 111-139 rag/100 ml to an intermediate group, and those with FBG values ~- 140 rag/100 ml on two separate occasions to the diabetic group 20 Assessment of DD was done by examination of both hands. The severity was determined by the degree of flexion deformity. The finding of a thickened band of the palmar fascia was classified as 'mild', definite flexion deformity as 'severe' contraeture. Patients with DD were questioned about the awareness of the deformity and its duration.

Key-words: Diabetes melIitus, Dupuytren's disease. Received: September 24, 1976. Acta diabet, fat. 14, 170, 1977.

170

M. RAVID, Y. DtNAI, E. SOHAR

RESULTS Among the patients admitted to the departments of medicine there were 110 patients with DM, 1,396 non-diabetic patients and 154 patients in the intermediate group. DD was found in 17 diabetics (15.45%), 9 non-diabetic patients (0.64%), and in 7 patients in the intermediate group (4.55%). Among the patients attending the DM clinics, DD was found in 152 cases (17.9%). These data together with age distribution, male/female ratio, and data about the DD patients are summarized in tab. 1. An oral glucose tolerance test (OGTT) (100 g) was performed in 14 of the 16 patients with DD and without overt DM (the remaining 2 patients were discharged by their physicians without performing the OGTT). According to the criteria outlined by KRALL and ZORRILLA11; the glucose tolerance was reduced in 10 patients. Of the 4 patients with DD and normal glucose tolerance, 2 had positive family history of DM (a diabetic mother of one patient, a father and a sister of the other). The relative frequency of DD among all patients with DM was 17.6% (169 cases among 959 patients with DM). The difference between the relative frequency of DD among diabetic and non-diabetic patients was highly significant (p < 0.001)*. Altogether there were 185 patients with DD, among them DM was present in 179 (96.7%).

departments of medicine clinics for diabetes mellitus diabetics

non diabetics

~ntermediate

no. of patients age (years) M/F ratio

849 16-82 (mean 52) 0,88 (398/451)

I10 17-81 (mean 54) 0.95 (53/57)

154 23-9t (mean 56) 1.44 (91/63)

1,396 19-86 (mean 52) 1.8 (756/64O)

Dupuytren's disease no. of patients age {years) M/F ratio

152 (17,9%) 32-80 (mean 64) 1.14 (81/71)

17 (i5.4%) 34-79 (mean 63) 1.43 (10/7)

7 (4.55%) 43-82 (mean 70) 0.75 (3/4)

9 (0.64%) 42.83 (mean 66) 1.25 (5/4)

1.2 (83/69) 46 (30.2%) 0.27 (32/120)

1.13 (9/8) 6 (35.3%) 0.3 (4/13)

025 (3/4) 1 (14%) 0.17 (1/6)

0.8 (4/5) 2 (22%) 0,29 (2/7)

hand affected R/L ratio both hands severe/mild ratio

Table I - Dupuytren's disease in diabetics and in patients in departments of medicine.

There was an increase in the relative frequency of DD with increasing age from 2% among diabetics younger than 40 to 15% in the age group 40-60, and to 28% in patients older than 60 (tab. 2). These differences were highly significant (the)a-values were 50.05 and 22.89 respectively, with 1 d.f.: p < 0.001). DD was found in 11.8% of diabetic patients with hyperglycemia of less than 5 years duration, in 14.2% among diabetics with hyperglycemia of 5 to 10 years, in 27.3% among patients who had been hyperglycemic * The statistical analyses were performed by Noreen Goldman, Ph.D, from the Center for PopuIation Studies, Harvard University, Cambridge/Mass. 171

DUPUYTREN'S DISEASE IN DIABETES MELLITUS

diabetes mellims

Dupuytren's disease

age.group (years) no. of patients

Table

mean age (years)

no, of patients

mean age (years)

< 40

231

35

5 (2%)

38

41-60

326

51

49 (15%)

56

> 60

402

66

115 (28%)

2 -

groups.

Dupuytren's disease in diabetes mellitus. Relative frequency in different age-

for 10 to 15 years, and in 23.1% among patients with hyperglycemia known longer than 15 years. The relation between the relative frequency of DD and the duration of hyperglycemia was significant (X" 26.98 with 3 d.f.: p < 0.001). Since the patients with long-standing hypergIycemia were often the older patients, it was necessary to determine whether the relative incidence of DD was independently related to the duration of hyperglycemia or whether it w'as the secondary effect of age. A long-linear analysis 2 was, therefore, appIied to study the effects of both determinants simultaneously. The analysis, based on the data displayed in tab. 3, showed that, in fact, all interactions were significant at p < 0.001. The age of the patients and the duration of hyperglycemia were related to each other, and each was independently related to the relative frequency of DD. However, when patients over 60 years were omitted, duration of hyperglycemia was no longer an important factor and the only significant interaction was between age and relative incidence of DD (p < 0.001). Three hundred and ten diabetic patients were maintained on diet alone, 284 patients received oral hypoglycemic agents and 365 patients were treated

Dupuytren's disease duration hyperglycemia ( years )

age (years)

no. of patients

0-5

60

6-10

no. of patients

%

93 127 84

I I7 20

t.1 13.5 19.5

60

54 64 148

2 10 27

3.1 15.5 18.2

11-15

60

41 84 87

0 14 44

0 16.6 50,6

> 15

60

33

2 8 24

6.0 15.9 38.0

51

63

T a b l e 3 - Relative incidence of Dupuytreu's disease in patients with diabetes according to age-groups and duration of hyperglycemia.

172

M. RAVID, Y. DINAI, E. SOHAR

with insulin. The incidence of DD in these groups was 16.8%, 20.4% and 1698 respectively, and there was no significant correlation with the mode of treatment (Xa 2.33 with 2 d.f.). Very few of the patients remembered the time they had first become aware of the presence of DD and many were unaware of it altogether. No correlation of the onset of DD with the time of onset of hyperglycemia could, therefore, be found. There were 96 patients with severe chronic pulmonary disease; 21 of them had DM. DD was found in 4 patients with both chronic pulmonary disease and DM, and in none without DM. Among 14 patients with liver cirrhosis and 5 patients with epilepsy, none had DD. DISCUSSION In a non-selected population of 2,509 inpatients and outpatients, DD was found almost exclusively in association with DM. Among 185 patients with DD encountered in this study, DM was de~niteIy present in 179 (96.7%). Two of the remaining 6 patients had a strong family history of DM, and only 4 patients were allegedly non diabetic. The relative frequency of DD in patients with DM was I7.6%, significantly higher than in patients without overt diabetes. The relative frequency of 0.64% and 4.55% in the normoglycemic and intermediate groups most probably reflects a fraction (17.698) of patients with latent or chemical DM in these groups. OGTTs were not performed on the non diabetic hospital patients. The true number of diabetics is, therefore, unknown. Since approximately every sixth diabetic was found to have DD, one may calculate that the relative frequenw of DM among the normoglycemic patients would be 3.6% and in the intermediate group 26%. This frequency corresponds well to the expected frequency of DM in such a population 7. 10 In diabetics younger than 60, age was the only other factor that determined the relative incidence of DD. However, when the older patients were included in the statistical analysis there was a good correlation also with the duration of hyperglycemia both directly, and indirectly, through age. The high relative frequency of DD in women and relatively small preponderance of the right hand, virtually exclude manual labour or trauma as possible etiologic factors. No association with chronic pulmonary disease was found in our patients. The dear*cut association of DD with DM in our series may imply that DD is a non-hyperglycemic manifestation of DM. The presence of DD in a patient should, therefore, be considered a marker of DM, and call for an investigation of carbohydrate metabolism.

SU~LMARY Dupuytren's disease (DD) was demonstrated in 169 of 959 diabetics (17.6%) and in 9 of 1,396 non-diabetic patients (0,64%). One hundred and seventy-nine of the 185 patients with DD had overt or latent diabetes mellitus (96.7%). The relative frequency of DD increased with age, the conditions was seldom found under the age of 40. DD shouId be regarded as a non-hyperglycemic manifestation of diabetes mellitus and its presence in a patient should prompt the investigation of glucose metabolism.

173

REFERENCES

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Reqtrests fov rep~intsshordd he a~ldresseilto: MORDCHAI RAVID Department of Medicine, J a f a Hospital P.O.B. 3107J, Tel-Aviv - Israel