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Diabetes & Metabolism
Vol 25, N° 6  - novembre 1999
p. 507
Doi : DM-11-1999-25-6-1262-3636-101019-ART50
RESULTS

Huge progression of diabetes prevalence and incidence among dialysed patients inmainland france and overseas french territories. a second national survey six years apart.(uremidiab 2 study)
 

S. Halimi [1], D. Zmirou [2], P.Y. Benhamou [1], F. Balducci [2], Ph. Zaoui [3], M. Maghlaoua [3], D. Cordonnier [3]
[1] Services d'Endocrinologie Diabétologie et Nutrition, CHU de Grenoble,38043 Grenoble Cedex, France.
[2] CAREPS (Centre Alpin de Recherches Epidémiologiques et de PréventionSanitaire), CHU de Grenoble, 38043 Grenoble Cedex, France.
[3] Service de Néphrologie Transplantation, CHU de Grenoble, 38043 GrenobleCedex, France.

Abstract

In 1989, we conducted a survey (UREMIDIAB) on the prevalence of diabetes among thepopulation on Renal Replacement Therapy (RRT) in Mainland France (MF), the lowest of thedeveloped countries (6.9 %) with a North-South gradient (higher prevalence in the North).This highlighted a possible (genetical or nutritional) "new french paradox" inmainland France populations. In 1992 we conducted a similar study in the french (mainlynon caucasian) overseas territories (OT) hosting 3.2 % of the total french population, andobserved a prevalence of diabetes in RRT of 22.9 %. The frequency of diabetes mellitus asa cause of ESRD increasing worldwide, we conducted a second survey in year 1995, in MF andthe OT. This study, UREMIDIAB 2, included all of the 244 french dialysis centers. A"Center file" allowed us to determine the prevalence and incidence of diabetesin the french RRT population, (response rate 73 %). Then a "Patient medicalfile" (response rate 64.8 % for MF and 91 % for the OT) provided detailedinformations: type of diabetes (type 1 or 2), etiology of nephropathy, status of diabeticcomplications, family's geographic origin of the patient. In MF the prevalence ofdiabetics in RRT doubled within 6 years: 13.04 % vs 6.9 %, the incidence reached 15.7 %.In the OT the prevalence and the incidence reached 25.7 % and 35.6 %, respectively. Type 2diabetes represented 87 % and 93 % of the RRT diabetics in MF and the OT, respectively.Diabetic nephropathy was considered as the cause of renal failure in 91.3 % of type 1 and57.5 % of type 2 diabetics under dialysis. We found: 14.7 % of myocardial infarction, 12.7% of cerebral strokes, 17.6 % of amputations (extreme 37 % in some OT centers) among thisdiabetic RRT population. A North-East (higher prevalence) South-West (lower) gradient wasconfirmed. We conclude that, while an unusual low prevalence (¾ 13 %) of diabetics underdialysis persists in some parts of Mainland France, the total prevalence has been doubledwithin 6 years (1989/95) and that in Overseas Territories, hosting similar mixed bloodpopulations than USA (afro-caribbeans, asians, indians, micronesians and metis), the highincidence of diabetes in RRT has reached the US levels during the same period.

Abstract
Progression de la prévalence et de l'incidence du diabète parmi lesdialysés en France métropolitaine et dans les DOM-TOM. UREMIDIAB.2.

En 1989 nous avons conduit l'enquête UREMIDIAB sur la prévalence du diabète parmiles dialysés en France métropolitaine. Elle était alors la plus faible des paysdéveloppés (6.4 %) avec un gradient nord-sud (plus élevée dans le nord), constituantun autre « French paradox ». En 1992 nous avons mené une étude similairedans les DOM-TOM français (majoritairement non caucasiens) concluant à une prévalencede 22.9 % (presque 4 fois plus élevée) dont 92 % de diabétiques de type 2. Devantl'accroissement rapide et général du nombre des diabétiques en dialyse partout dans lemonde, nous avons entrepris une seconde enquête épidémiologique sur l'année 1995portant sur l'ensemble des territoires français, UREMIDIAB 2. Nous avons questionnél'ensemble des 244 centres de dialyse français (232 en métropole et 12 pour lesDOM-TOM). Un « dossier centre » a permis de déterminer la prévalence etl'incidence du diabète (taux de réponse de 73 %). Le « dossier patient »précisant le type de diabète, le statut des autres complications liées au diabète,l'origine de la néphropathie, l'origine géographique des patients ; (taux deréponse de 64,8 % en métropole et de 91 % dans les DOM-TOM). Les résultats de 1995montrent un doublement de cette prévalence, en 6 années, en France métropolitaine(13,04 %) et une incidence de 15,7 %. Dans les DOM-TOM, la prévalence atteint 25,7 % etl'incidence 35,6 % soit plus d'un patient dialysé sur trois. La proportion dediabètiques de type 2 était de 87 % en métropole et 93 % aux DOM-TOM. La néphropathieétait considérée comme due au diabète pour 91.3 % des diabétiques de type 1 et 57.5 %des diabétiques de type 2. On dénombre 14,7 % d'infarctus du myocarde, 12.7 %d'accidents vasculaires cérébraux, 17.6 % d'amputations (jusqu'à 37 % dans des centresdes DOM-TOM). Un gradient nord-est (haute prévalence)/sud-ouest (plus faible prévalence)est confirmé. Nous concluons que la France comporte encore dans certaines régions deszones de faible prévalence de diabétiques parmi les dialysés (¾ 13 %), mais en moyennecelle-ci s'est considérablement accrue en 6 années (X2) rejoignant dans plusieursrégions les niveaux des pays voisins (>= 20 %). Dans les DOM-TOM l'incidence de plusde 35 % atteint les niveaux très élevés enregistrés aux USA pour des populationssimilaires (origine africaine, indienne, asiatique et européenne).


Mots clés : Diabète. , insuffisance rénale terminale. , dialyse. , épidémiologie. , DOM. , TOM.

Keywords: End-stage renal failure. , renal replacement therapy. , diabetes. , epidemiology.


SUBJECTS AND METHODS

Diabetes mellitus has become the leading cause of end-stage renal disease (ESRD) andrenal replacement therapy (RRT) in all developed countries [ [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]]. Although incidence andprevalence of terminal renal failure in diabetic patients greatly vary from country tocountry, in the recent past, the majority of registries documented a progressive increaseof diabetic patients on RRT. The proportion of the diabetics amongst the whole populationin RRT is higher in Northern Europe and in the USA and lower in Central and SouthernEurope. Moreover, the distribution of types of diabetes mellitus (i.e., type 1 and type 2diabetes) varies with geographic and genetic background. In 1989, our group conducted anational epidemiological study in Mainland France to compare the situation in our countrywith international data. This survey concluded that the prevalence of end-stage renaldisease in diabetic patients in France was the lowest, 6.9 %, [ [18]] of Western Europe [ [14]] and four to five times lowercompared to North America [ [15], [16]], representing a new frenchparadox. In 1992, we performed an additional trial to measure the prevalence of RRT due todiabetes in the overseas french territories (OT). These territories, representing 3.2 % ofthe total French population, are distributed across the world and their populationsessentially are non-Caucasian (mixed blood population) with a higher prevalence ofdiabetes mellitus, mostly type 2. We found a prevalence of 22.9 % [ [21]] of diabetes amongst patientson dialysis in these populations, 3 times higher than the mainland prevalence.

Thus we decided to perform a new survey (1995) in mainland France aiming to see whetherthe huge increase of the prevalence of type 2 diabetes mellitus in RRT described in allother developed countries was also observed in our country or whether french"specific situation" remained unchanged. Additionaly, our first survey describedan influence of the geographical distribution of the patients in mainland France, i.e, ahigher prevalence of RRT in diabetic patients in the northern part of the country and alower one in the southern part [ [18]].Other additional studies were performed in this second trial, mainly to describe the usualmanagement of diabetic patients in RRT in our country. This study was also conducted inthe overseas french territories population.

The study population involved all the patients treated by dialysis of any kind in allthe 244 public or private dialysis units listed in the 1993 AURA (Association for the Useof Artificial Kidneys) directory for mainland France (n = 232) and overseas territories (n= 12). There were two phases in the study. First, a prevalence and incidence study wasperformed. A form was mailed to heads of the units who were asked to record the totalnumber of patients treated for dialysis during the last two days of year 1995, to identifythose who were diabetic (prevalence) and to classify them according to the type ofdiabetes mellitus (type 1 or type 2). This classification was made by the nephrologist ofeach center according to an algorithm that had previously been established and validatedby our group in the UREMIDIAB 1 study, based on age at diagnosis, body mass index anddelay for insulin introduction (19). They were also asked to number the new dialysedpatients (total and diabetics, including type of diabetes) for the year 1995, allowing tocalculate the incidence of diabetes mellitus, amongst the total dialysed population. Thisconstituted the "Center File".

The second phase of the study provided detailed informations regarding the diabeticpopulation under dialysis and constituted the "Patient File". This second formcontained the following informations

  • The clinical status of the patient and the history of diabetes were recorded, allowing to determine the type (type 1 or type 2) of diabetes according to the algorithm previously validated and published by our group [ [19]].
  • The family's geographic origin of the diabetic patient and informations on the area where the family and/or the patient spent the longest part of their life. These data were required to address the question of a genetic or environmental influence on RRT diabetic prevalence heterogeneity previously described in mainland France by our group [ [18]].
  • Also recorded was the presence of other diabetic subjects and nephropathies in the family of every diabetic dialysed patient.
  • The status of diabetic complications was collected: retinopathy, cerebral stroke, amputations, coronary heart disease.
  • In order to determine the etiology of nephropathy (diabetic glomerulosclerosis, other or both), each record was rewieved by one of us (DC) on the basis of a list proposed to each head of dialysis unit . Finally, type and duration of RRT were collected, as well as any history of previous kidney and/or pancreas transplantation.

Stastical analysis

- The prevalence and the incidence rates ofdiabetes mellitus in the dialysed population were calculated for each type of diabetes.Standard statistical tests were used to compare subgroups of the study population (Chisquare test, Student's test). To assess the geographical distribution of diabeticnephropathy cases, we compared the mean prevalence and incidence rates of type 1 and type2 diabetes mellitus among the 22 regions of mainland France and overseas territories usingthe 22 corresponding state official classification. The analysis was conducted with anIBM-PC computer using the SPSS/PC + statistical package (SPSS Inc.Chicago, 1988).

Prevalence and Incidence(Table I

andII)

- One hundred and eighty oneunit files were returned to determine the prevalence and incidence of diabetic patientsunder dialysis. The mean response rate was 73 %. The response rate ranged from 33 % in oneregion in Mainland, with a large majority of mainland regions responding between 60 and 80% to 91.7 % in overseas territories. No particular characteristics emerged from the unitsthat did participate in the study. However, unit size and geographical location did notdiffer bteween responding and non responding centers. Amongst the responders (178/244),twenty three did not return the patient file. This allows to determine the diabeticpatients characteristics for 64.8 % of the dialysis unit and for 91 % of them in theoverseas territories. The unit characteristics did not differ between the centers thatparticipated in the second (patient file) phase of the study, and those that did not. Thenumber of patients (total dialysed and diabetic dialysed) per center was higher in the nonresponding centers: n = 107.4 vs n = 87.7 (p = 0.11) and 14.7 vs 12.5 (p = 0.58),respectively, but these differences were not significant. The total population receivingdialysis in the participating units was 16.174 patients, 2303 of whom were diabetic (14.24%). In mainland France, 1915 diabetics were found amongst 14.666 dialysed patients (13.05%) vs 388 diabetics amongst 1508 in overseas territories (25.72 %). Of these dialyseddiabetic patients, 13.05 % (n = 270) were classified as type 1 and 87 % (n = 1666) as type2 in mainland France and 7.5 % (n = 29) vs 92.5 % (n = 359) in overseas territories (Table II)

. However, 70 % ofdiabetics in RRT were treated with insulin. The sex ratio M/F was 1.1 (52 % male) for alldiabetes types and geographic regions. The total incidence of diabetic patients admittedin dialysis for year 1995 was 17.15 % (670/4500). This incidence was 15.7 % (6.45 to 25 %)in mainland and 35.61 % in overseas territories. The mean age of type 1 or type 2diabetics in RRT was 44.7 ± 10 years and 66.5±9 years, respectively. Thus the totalincidence of RRT in the french general population during 1995 can be 7.9 fold higher indiabetic patients. This corresponds to an RRT admission rate of 46 diabeticpatients/million (ppm) vs 382 patients/million for all causes of RRT. When separatelycalculated for type 1 and type 2 diabetic patients, this ratio is 8- and 7.3- fold higher,respectively, when compared to the non-diabetic population.

Among the 1925 (83.5 %) completely fulfilled patient forms, 827 diabetics in RRT (42.9%) reported a diabetic (first and second degree) parent in their family and 18.5 % of themwere known to suffer from some nephropathy.

The status of diabetes-linked complications

was studied forretinopathy, coronaropathy, amputations and cerebral stroke. Among type 1 diabetics, 97 %presented with one or more of these complications vs 84 % among type 2 diabetics. Thepercentage of patients with complications reached 91.4 % in OT although the majority ofthem were type 2 diabetics. Retinopathy was present in 71.7 % of the whole french diabeticRRT population and in 80 to 100 % of patients in the OT dialysis centers. A recent (<12 months) myocardial infarction (MI) was present in 2.7 % of the patients, and a notrecent (> 12 months) one in 14.7 % of them. Cerebral stroke was present in 12.3 % ofthe whole diabetic RRT population, without any influence of the geographic region (from11.5 to 14.1 %). The mean prevalence of amputations was 17.6 % in the whole diabetic RRTpopulation, from 5.9 % in one mainland dialysis center to 37 % of the patients in someothers (overseas territories). A large majority (81.4 %) of diabetics in RRT had 1 or 2other diabetic complications.

The origin of the ESRD

- was considered as a diabetic nephropathy in91.3 % of type 1 and in 57.5 % of type 2 RRT diabetics. The main other causes supposedlyresponsible for ESRD in type 2 RRT diabetics were: chronic vascular nephropathy in 12.4 %,interstitial and tubular nephropathy in 6.6 %, and different other diseases(glomerulonephritis, polycystic kidney disease) in 13.2 %.

Geographic distribution of the diabetics in RRT

- in mainland France (Fig. 1)

. Among the 22administrative regions of our country, a North-South gradient was observed in this study.In 80 % of dialysis centers located in the north-east (N-E) of France, the prevalence ofdiabetics exceeded 16 % (16.34 to 17.94 %), in 75 % located in the south-west (S-W) ofFrance this prevalence was lower than 13 % (8.22 to 12.78 %). However there were someexceptions, as a low prevalence (11.8 %) in Lorraine (N-E). This could be explained by alow survival rate in RRT, the incidence being 16.74 % in this region. By contrast, ahigher incidence (21.93 %) in Midi-Pyrénées (S-W) was also found. No gradient wasobserved for the geographical distribution of type 1 diabetics in RRT. A North-Southgradient was found for the type 2 diabetes in RRT that was mainly explained when the placeof birth of the patients was taken into consideration. This was confirmed when the placeof birth of the parents (the father, or the mother or both parents) was taken intoaccount. Dialysis centers situated in Paris area showed a special distribution for theorigin of the parents of the diabetic patients in RRT due to the large number of migratingpatients coming from other regions, OT or foreign countries.

The duration on RRT

- in the whole population ranged between 1 to 4years for 72 % of the prevalent diabetic patients, 5 to 7 years for 17.4 % and over 7years for 10.6 %.

Modalities of Renal Replacement Therapy (RRT)

- hemodialysis (HD) wasused by 70.2 % of type 1 and 75.8 % of type 2 diabetics in RRT. Self hemodialysis and homedialysis was used by 8.9 %. Peritoneal dialysis (PD) was used by 13.6 % of diabetics.

DISCUSSION

In our previous survey in mainland France (UREMIDIAB 1, 1989), we observed the lowestprevalence (6.9 %) of diabetes among patients receiving dialysis when compared to all theother developed countries [ [18], [19], [20]]. During year 1992, weconducted a complementary survey in the overseas territories populations [ [21]]. We found a prevalence of 22.9% of diabetes among all RRT patients with a proportion of 92 % of type 2 diabetics. Thisprevalence, close to that of non-white US citizens, involved mixed populations (afrocaribeans, asians, indians, micronesians and metis), a similar ethnic make-up of mixedpopulations [ [15], [16]] as in Australia andNew-Zealand [ [11]]. Our presentstudy shows a progression of diabetes as a cause of ESRD and subsequently RRT in mainlandFrance. The prevalence was doubled (6.9 to 13.05 %) between the two studies (6 years), andalthough the number of responding dialysis centers was lower for the second survey (73 vs80.4 %), the absolute number of diabetics in RRT grew from 884 to 1915 patients (+ 116 %,+ 20 % per year). Thus, the increase of diabetics in RRT was higher than 2-fold, while thetotal number of RRT in mainland France increased by 25 %. This huge increase mainly is dueto the progression of type 2 diabetics in RRT: 80 to 87 % of all dialyzed diabetics and705 to 1,666 patients (+ 136 %, + 22.6 % per year). Meanwhile, the absolute number of type1 diabetics in RRT increased from 179 to 249 (+ 39 %, + 6 % per year). The epidemiologicalvalue of this study is validated since the size and geographical location of respondingand non responding dialysis centers were not significantly different. We can furtherextrapolate to a total general RRT population of 22,156 patients, amongst them 341 type 1and 2,282 type 2 diabetics. The incidence for year 1995 showed a further increase: 15.7 %in mainland France, ranging from 6.45 to 25 % according to the studied region. Theanalysis of the geographical prevalence and incidence distribution confirmed the gradientpreviously described in UREMIDIAB 1 study: higher for the north-east part and lower in thewest, south and south-east of the country. This gradient was due to type 2 diabetics andvalues recorded for the french regions were close to those of the adjacent countries [ [1], [2], [3], [4], [5], [7], [9], [12], [14]]: Belgium incidence 21.5 %(1997), Austria 18 % (1996), Lombardy 11 % (1992), Catalunya 16.6 % (1997). The number ofprevalent diabetics in RRT may be underestimated in Germany: 22 % [ [1]]. During the same period, for theHeidelberg region, this prevalence reached 59 % in 1995 [ [7]]. For the Hanover region, thisprevalence was about 47 % in 1997 [ [5], [23]]. Thus, while theprogression of diabetic patients in dialysis in mainland France was dramatic between 1989and 1995, the ppm remained the lowest of the developed countries with Lombardy 46 and 59ppm respectively (Table III)

. We tried to analyze geographical differences to determine whether they were due toethnic or environmental origins. Our data showed that outside the Paris area, diabeticpatients were mainly dialysed in their family's original geographical location. This doesnot allow to explain the geographical differences confirmed by the present study. The highprevalence observed in the overseas territories in 1992 was confirmed 3 years later with aslow progression of the prevalence (25.72 % vs 22 %). However, the high level of incidencein 1995 (35.61 %) in OT was comparable to that of the non-white US citizens [ [16]]. This discrepancy betweenincidence and prevalence in OT probably is due to a rather short survival of diabeticpatients in dialysis [ [22], [24]], the majority of them beingtype 2, older and multicomplicated diabetics. This incidence of diabetes in RRT iscomparable to that of African Americans [ [16]] and to that of asianpopulations, Aborigenes in Australia (41 %), Maories in New-Zealand (61 %) and Pacificislanders (49 %) [ [10], [11]].

This progression of the diabetics in RRT partly is due to the rise of the prevalence oftype 2 diabetes, linked to the the general population aging and, more importantly, to thecontinuous improvement of care and survival in type 2 diabetics during the last decade [ [17], [22]]. This is mainly the result ofantihypertensive therapy and treatment of coronary heart disease. One can predict thisphenomenon to increase in the next decade. This would emphazise a continuous improvementof survival of diabetic patients on dialysis treatment, which remains very short. The highmortality of these patients mainly is due to cardiovascular disease. The first cause ofdeath is myocardial infarction (MI) (62 % of deaths). Mortality is 4.8- in type 1 and3-times higher in type 2 diabetics compared to non diabetic RRT patients. A majority oftype 2 diabetics in RRT exhibits two or three severe complications. Although thesediabetic patients in dialysis are type 2 elderly polymorbid patients, it is noteworthythat a few of them are listed for kidney transplantation when compared to other europeancountries [ [25]]. Finally, it isremarkable to note that in our present study, the relative risk of RRT compared to thegeneral population appeared similarly high in type 2 diabetes (7.3-fold) and type 1diabetes (8-fold) [ [26]].

In conclusion, this second french survey confirms the silent epidemic of ESRD indiabetic patients and mainly emphasizes the dramatic human and economical cost of type 2multicomplicated diabetes, as it is worldwide. On the other hand, we confirm a relativelylower prevalence of diabetes among ESRD patients, mainly in the western and southernregions of mainland France, possibly linked to genetical or environmental factors.

Multiple efforts are needed in the treatment of diabetic patients and mainly type 2diabetics, as recently suggested by the UKPDS trial [ [27], [28], [29]], that showed the frequency ofmicroangiopathic complications could be reduced by a tight glycemic control and, moreimpressively, by an intensified antihypertensive treatment. Moreover, kidneytransplantation must be developed for ESRD diabetic patients and mainly for type 2diabetics [ [25]].

Acknowledgements

This study was supported by a grant from ALFEDIAM-Novo Nordisk France, 1995. We would like to thank all doctors and staff of the AURA who have contributed their data to the UREMIDIAB and UREMIDIAB 2 studies by completing the questionnaires.

Figure 1.

Geographic distribution in the french regions of the incidence ofdiabetic patients in Renal Replacement Therapy.

*A.S.B.L: Groupement des néphrologuesfrancophones de Belgique pmp = per million population

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