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Risk Factors for Type 2 Diabetes in Women Attending Menopause Clinics in Italy: a Cross-Sectional Study

Posted on: Sunday, 18 September 2005, 03:00 CDT

ABSTRACT

Objective To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause.

Subjects Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms.

Methods Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year.

Results Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged ≥ 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/ university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73).

Conclusions This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

Key words: DIABETES, WOMEN, MENOPAUSAL STATUS

INTRODUCTION

Type 2 diabetes is a common condition and one of the main determinants of cardiovascular disease risk. Epidemiological studies have shown that the frequency of type 2 diabetes increases with age and that overweight, low socioeconomic status and low physical activity are among the main risk factors1-5.

Few studies have analyzed the epidemiological characteristics of diabetic women. In particular, around menopause, there is an increase in the frequency of the disease and marked changes in risk factors for cardiovascular diseases6,7. Epidemiological data are also limited on the relationship between menopausal status, age and diabetes, and evidence is inconsistent on the effect of hormonal replacement therapy (HRT)8,9. In some studies, the prevalence of HRT use is lower among diabetic women10; however, this may be due to selective mechanisms. Otherwise, it has been suggested that HRT users with diabetes are at greater risk of ischmie diseases than non- users with diabetes11, but available data are controversial8,9.

Most studies on the determinants of type 2 diabetes in women have been conducted in North American and European populations. However, determinants may differ in countries with different lifestyles and prevalence of HRT use10. In order to gain information from a Southern European population, we analyzed data from about 50 000 women attending menopause clinics in Italy for routine counselling10,12-15

The analysis of the effect of menopause on the risk of type 2 diabetes and the risks of cardiovascular disease are of relevance to the findings from the Women's Health Initiative study16, which did not confirm previous suggestions of a reduced risk of cardiovascular disease in HRT users17.

PATIENTS AND METHODS

Between 1997 and 2000, we conducted a large cross-sectional study on the characteristics of women around the menopause attending a network of first-level outpatient menopause clinics in Italy for general counselling or treatment of menopausal symptoms10,13-15. Women observed consecutively during the study were eligible. The protocol did not set any exclusion criteria.

All women who agreed to participate underwent a gynecological examination and were asked about their general characteristics and habits, reproductive and menstrual history and selected medical history. Their weight (kg) and height (cm) were recorded.

The study started in 1997 in 25 centers, increasing to 268 centers in 1999. Of these, 63 were in the north, 81 in the middle and 124 in the south of Italy. A total of 49122 women (mean age 53 years) entered the study. The mean number per center was 98. Eess than 3% of eligible women refused to participate. Information on diabetes was available on 44694 women (91.0%).

Type 2 diabetes was defined according to National Diabetes Data Groups Indications18 (evaluation of C-peptide was not mandatory). Fasting blood glucose on an oral glucose tolerance test during the previous year was considered for the diagnosis.

During the interview, blood pressure was measured three times on the right arm, with the participant seated. Women for whom the mean of the second and third diastolic blood pressure values taken during the interview was > 90 mmHg and women reporting any current pharmacological treatment for elevated blood pressure were considered hypertensive. The finding of elevated blood pressure was checked by the physician against clinical records.

Body mass index (kg/m^sup 2^) was classified on the basis of the best possible approximation of tertiles of body mass index for the whole population.

Postmenopausal women were defined as those with surgical menopause (i.e. bilateral oophorectomy with or without hysterectomy), women aged > 55 years who had undergone hysterectomy without bilateral oophorectomy, together with those whose menstrual cycles had stopped more than 1 year before interview.

Regular physical activity was defined as 3 or more hours per week.

Data analysis

Odds ratios (OR) of type 2 diabetes and the corresponding 95% confidence intervals (CI) were computed. To take account of the potential reciprocal confounding effects of the variables considered, factors significantly related with diabetes risk in the age-adjusted analysis were subsequently included in multiple logistic regression models fitted by the method of maximum likelihood19. The terms included are indicated in the footnotes to the tables.

RESULTS

Of the 44 694 women who entered the study, 808 had a diagnosis of type 2 diabetes (1.8%). The distribution of women with and without type 2 diabetes according to selected general characteristics is shown in Table 1.

The OR for diabetes increased with age. Compared with women aged < 50 years, the multivariate OR for diabetes was 1.31 for women aged 50-52 years, 1.66 at 53-56 years and 2.84 in women aged ≥ 57 years.

Table 1 Odds ratios of diabetes according to selected factors

Being overweight was associated with an increased risk of diabetes. In comparison with body mass index < 24, the multivariate OR was 1.95 for a body mass index of 24-26 and 4.29 for women with a body mass index > 26. A history of hypertension increased the risk of diabetes.

Diabetes was less frequent among more educated women (OR high school/university vs. primary school, 0.44).

Physical activity was associated with a lower risk of diabetes. No association emerged between parity and risk of diabetes.

In comparison with premenopausal women, the OR for diabetes was 1.38 in women with a natural menopause.

There was no clear association between age at menopause and risk of diabetes. The OR for diabetes for current HRT use was 0.58, but no relation was found between the duration of HRT use (data not shown), smoking or alcohol intake and risk of diabetes

We analyzed the effect of age, body mass index, history of hypertension and physical activity in strata of pre- and postmenopausal women (Table 2). No marked differences in the estimates of OR emerged. In particular, the risk of diabetes increased with age both in pre- and postmenopausal women.

DISCUSSION

Epidemiological evidence on the role of female hormones in type 2 diabetes is inconclusive, and the effect of HRT in particular is still debated. The recent Heart and Estrogen/progestin Replacement Study (HERS) suggested that HRT may reduce the development of type 2 diabetes9. A more recent study has suggested that HRT increases the risk of cardiovascular disease in diabetic women11.

Table 2 Odds ratios[dagger] (and 95% confidence intervals) of diabetes according to selected factors in strata of preand postmenopausal women

In our study, HRT users were at lower risk. In interpreting the relation between HRT and diabetes, potential selective bias should be considered as some physicians may be wary of prescribing HRT to diabetic women10.

In this study, after taking into account the potential confounding effect of age, we observed an increased risk of diabetes in postmenopausal women. Women with a spontaneous menopause were at increased risk of diabetes in all age strata, suggesting that the menopausal status is an independent determinant of diabetes risk. However, we did not find any association between diabetes risk and surgical menopause, thus sug\gesting that the effect of menopause on diabetes risk is complex.

Body weight is a recognized determinant of diabetes1, but the effect is different in pre- and postmenopausal women. This point is also of interest in the debate regarding menopause and body weight20- 24. Our study found that, with increasing body mass index, the risk of type 2 diabetes also increased, but we did not observe any difference in the OR estimates of diabetes for high body mass index with menopausal status.

Studies in different populations have shown that a low level of physical activity is related to a higher frequency of diabetes4,5 which we have confirmed. One limitation of the analysis is the fact that physical activity was self-reported; however, any misclassification should tend to underestimate the ORs. The protective effect of physical activity was similar in pre- and postmenopausal women. Likewise, a lower frequency of diabetes in more educated women has been reported in other studies25.

Potential limitations should be carefully considered. First of all, the women analyzed were part of a large study whose main goal was to describe the characteristics of women attending first-level outpatient menopausal clinics in Italy. Thus, they cannot be considered representative of the Italian population but are presumably particularly interested in health and specifically menopause-related problems. Furthermore, women with combined risk factors for cardiovascular disease (e.g. diabetes, hypertension and hypercholesterolemia) are probably much more likely to be seen by second-level centers than patients with only one risk factor. However, the prevalence of type 2 diabetes was about 2%, which is similar to that of the general population in the same age strata26. In any case, the aim of this analysis was to evaluate determinants of diabetes in women around menopause. Thus, any inference must be made in strictly comparative terms. The study started in 1997; thus we used diagnostic criteria commonly used at that time. In order to maintain similar criteria during the study, we decided not to follow the more recent criteria published by the American Diabetes Association27.

The strengths of the study include the fact that it provides an opportunity to analyze the determinants of type 2 diabetes in a large series of women.

In conclusion, this large cross-sectional study suggests that, after taking into account the effect of age, postmenopausal women are at a higher risk of developing type 2 diabetes. Other main determinants of risk of type 2 diabetes among women around menopause were low socioeconomic level, being overweight, a low level of physical activity, and hypertension. The effect of these factors was not different in pre- and postmenopausal women.

ACKNOWLEDGEMENTS

The following clinicians are co-authors of this paper: Participating Centers: Cento (P. Di Donato); Cattohca (N.A. Giulini); Parma (A. Bacchi Modena); Forli (G. Cicchetti); Reggio Emilia (G. Comitini); Bologna (G. Gentile); S. Lazzaro di Savena (P. Cristiani); Sassuolo (A. Careccia); Lugo di Romagna (E. Esposito); Reggio Emilia (F. Gualdi); Bazzano (S. Golinelli); Scandiano (E. Bergamini); Carpi (G. Masellis); Rimini (S. Rastelli); Gorizia (C. Gigli); Trieste (A. EHa); Udine (D. Marchesoni); Udine (F. Sticotti); S. Daniele del Friuli (G. Del Frate); Palmanova (C. Zompicchiatti); Ea Spezia (E. Marino); Geneva (M.R. Costa); Genova Voltri (P. Pinto); Eavagna (D. Dodero); Genova (A. Storace); Genova (G. Spinelli); Milano (S. Quaranta); Como (C.M. Bossi); Mantova (A. Ollago); Brescia (U. Omodei); Milano (M. Vaccari); Eodi (M. Euerti); Treviglio (F. Repetti); Magenta (G. Zandonini); Milano (F. Raspagliesi); Sondrio (F. Dolci); Milano (G. Gambarino); Sondalo (B. De Pasquale); Vimercate (G. Polizzotti); Saronno (G. Borsellino); Melegnano (P. Alpinelli); Eecco (N. Natale); Sesto S. Giovanni (D. Colombo); Como (C. Belloni); Brescia (A. Viani); Paderno Dugnano (G. Cecchini); Bollate (G.W. Vinci); Brescia (B.A. Samaja); Manerbio (E. Pasinetti); Milano (M. Penotti); Como (F. Ognissanti); Cremona (P. Pesando); Ivrea (C. Malanetto); Torino (M. Gallo); Torino (G. Dolfin); Moncalieri (P. Tartaglino); Bra (D. Mossotto); Alessandria (A. Pistoni); Alba (A. Tarani); Cuneo (P.D. Rattazzi), Novara (D. Rossaro); Pinerolo (M. Campanella); Trento (E. Arisi); Rovereto (M. Camper); Aosta (D. Salvatores); Soave-Tregnago (E. Bocchin); Trccenta (G. Stellin); Treviso (G. Meli); S. Don di Piave (V. Azzini); Isola delia Scala (F. Tirozzi); Mestre (G. Buoso, R. Fraioli); Treviso (V. Marsoni); Pieve di Cadore (C. Cetera); Vicenza (R. Sposetti); Vittorio Veneto (E. Candiotto); Portogruaro (R. Pignalosa); Motta di Livenza (L. Del Pup); Chieti (U. Bellati); Atri (C. Angeloni); Eanciano (M. Buonerba); Vasto (S. Garzarelli); Pescara (C. Santilli); Ortona (M. Mucci); Penne (Q. Di Nisio), E'Aquila (F. Cappa); Pescara (I. Pierangeli); Teramo (A. Cordone); Agnone (L. Falasca); Campobasso (D. Ferrante); Roma (G.B. Serra); Roma (E. Cirese); Roma (P.A. Todaro); Roma (C. Romanini); Roma (L. Spagnuolo); Roma (A. Lanzone); Roma (C. Donadio); Roma (M. Fabiani); Alatri (E. Baldaccini); Roma (S. Votano); Latina (P. Bellardini); Velletri (W. Favale); Anzio (V. Monti); Roma (A. Bonomo; C.E. Boninfante); Roma (P. Pietrobattista); Senigallia (L. Massacesi); Pesaro (G. Donini); Ancona (F. Del Savio); Macerata (L. Palombi); Ascoli Piceno (P. Procaccioli); Fabriano (A. Romani); Osimo (G. Romagnoli); Pisa (A.R. Genazzani, M. Gambacciani); Firenze (G. Scarselli); Prato (P. Curiel); Siena (V. De Leo); Pescia (A. Melani); Montevarchi (V. Levi D'Ancona); Borgo S. Lorenzo (G. Giarr), Poggibonsi (E. Di Gioia); Lucca (P. Ceccarelli); Firenze (G.B. Massi); Livorno (S. Cosci); Bagno a Ripoli (G. Gacci), Sansepolcro (A. Cascianini); Perugia (C. Donati Sarti); Foligno (S. Bircolotti); Citt di Castello (P. Pupita); Perugia (M. Mincigrucci); Narni (A. Spadafora); Iglesias (G. Santeufemia); Oristano (G. Marongiu); Sassari (G.R. Lai); Olbia (R. Lai); Sassari (S. Dessole); Potenza (S.A. D'Andrea); Villa d'Agri (Coppola); Napoli (A. Chiantera); Napoli (De Placido); Napoli (R. Arienzo); Solofra (A.R. Pastore); Napoli (A. Tamburrino); Napoli (A. Cardone, N. Colacurci); Benevento (S. Izzo); Napoli (R. Tesauro); S. Maria Capua Vetere (A. Pascarella); Nocera Inferiore (M.G. De Silvio); Napoli (L. Di Prisco); Napoli (N. Lauda); Napoli (F. Sirimarco); Aversa (C. Agrimi), Mercogliano (G. Casarella); Eboli (G. Senatore); Oliveto Citra (S. Ronzini); caserta (G. Ruccia); Giugliano (G. De Carlo); Battipaglia (G. Pisaturo); Castellammare di Stabia (F. Carlomagno); Salerno (A. Fasolino); Napoli (F. Fionllo); S. Bartolomeo m Galdo (R. Sorrentino); Vico Equense (V.B. Ercolano); Napoli (S. Panariello); Pozzuoli (A. Brun); Reggio Calabria (P. Tropea); Castrovillari (C.M. Stigliano); Cosenza (A. Amoroso); Soveria Mannelli (P. Vadal); Oppido Mamertina (A. Coco); Soriano Calabro (G. Galati); Lamezia Terme (G. Barese); Crotone (G. Masciari); Corigliano (P. Pirillo); Soverato (T. Gioffr); Catanzaro (P. Mastrantonio); Catanzaro (A. Cardamone); Trebisacce (N. D'Angelo); Paola (G. Valentine); Crotone (R. Barretta); Gioia Tauro (G. Ferraro); Mesagne (C. Ferruccio); Terlizzi (D. Agostinelli); Cerignola (G. Corrado); Foggia (A. Scopelliti); Bari (S. Schonauer, V. Trojano); Taranto (F. Bongiovanni); Lecce (F. Tinelli); Brindisi (E.R. Poddi); Poggiardo (F. Scarpello); Altamura (L. Colonna); Castellaneta (G. Fischetti); Carbonara (R. Doria); Barletta (G. Trombetta); Grottaglie (E.B. Cocca, A. D'Amore); Castellana Grotte (M. Di Masi); Acquaviva delle Fonti (R. Liguori); Francavilla Fontana (A. Dimaggio); Taranto (M.R. Laneve); Martina Franca (M.C. Maolo); San Severe (G. Gravina); S. Pietro Vernotico (G. Nacci); Catania (F. Nocera); Palermo (A. Lupo); Palermo (C. Giannola, R. Graziano); Palermo (M. Mezzatesta); Palermo (G. Vegna); Enna (G. Giannone); Catania (G. Palumbo); Messina (F. Cancellieri); Milazzo (A. Mondo); Messina (A. Cordopatri); Caltanisetta (M. Carrubba); Leonforte (V. Mazzola); Caltagirone (L. Cincotta); Comiso (S. D'Asta); Mazara del Vallo (A. Bono); Canicatti (L. Li Calsi); Catania (S. Cavallaro Nigro); Vittoria (S. Schiliro); Messina (A. Repici); Palermo (D. Gullo); Mussomeli (A. Orlando); Grammichele (F. Specchiale); Piazza Armerina (A. Papotto). Regional Coordinators: Angeloni (Abruzzo), D'Andrea (Basilicata), Stigliano (Calabria), Arienzo (Campania), Di Donate (Lmilia), Giulini (Romagna), Gigli (Friuli Venezia Giulia), Todaro (Lazio), Marino (Liguria), Luerti (Lombardia), Donini (Marche), Ferrante (Molise), Dolfin (Piemonte), Poddi (Puglia), Santeufemia (Sardegna), Nocera (Sicilia), Melani (Toscana), Arisi (Trentino Alto Adige), Mincigrucci (Umbria), Salvatores (Valle D'Aosta), Bocchin (Veneto). National Coordinators: A. Massacesi, A. Chiantera, C. Donati Sarti, P. De Aloysio, U. Omodei, F. Ognissanti, C. Campagnoli, M. Penotti, A. Gambacciani, A. Graziottin, C. Baldi, N. Colacurci, G. Corrado Tonti. Data analysis: F. Parazzini, L. Chatenoud.

Conflict of interest Nil.

Source of funding The study analysis was partially supported by an educational grant from Bracco, Italy.

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Gruppo di Studio Progetto Menopausa Italia

Correspondence: Dr F. Parazzini, AOGOI, via Abamout 1, 20100 Milan, Italy

Received 16-07-04

Revised 26-04-05

Accepted 25-05-05

Copyright CRC Press Sep 2005

Source: Climacteric

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