Download - Risk Factors for Lower Limb Complications in Diabetic Patients

Risk Factors for Lower Limb Complicationsin Diabetic PatientsMedhat El-Shazly, Moataz Abdel-Fattah, Nicola Scorpiglione, Massimo Massi Benedetti, FabioCapani, Fabrizio Carinci, Quirico Carta, Donatella Cavaliere, Eugenio M. De Feo, ClaudioTaboga, Gianni Tognoni, Antonio Nicolucci, on behalf of The Italian Study Group for theImplementation of the St. Vincent Declaration

ABSTRACT

Diabetic lower extremity complications may be predictor of lower extremity complicationscompared to NIDDM patients not being treatedinfluenced by a number of factors, including those

related to the interaction between patients and the with insulin. Cardio-cerebrovascular disease andpresence of diabetic neuropathy were associatedhealth-care system. Our objective is to identify risk

factors for the development of lower limb with a higher risk of being a case (OR 5 1.4,CI 1.2–1.8 and OR 5 3.0, CI 2.1–4.2, respectively).complications, by looking for classical clinical

variables and those related to quality of care. A Patients who needed help to reach the healthfacility before the onset of the complications andcase-control study was carried out between

December 1993 and June 1994 by interviewing 348 those who did not attend health facilities regularlywere more liable to develop complications (OR 5patients with lower-limb diabetic complications

and 1050 controls enrolled from 35 diabetes 1.5, CI 1.1–2.2 and OR 5 2.0, CI 1.3–3.0,respectively). Patients who had never receivedoutpatient clinics and 49 general practitioner’s

offices in Italy. Among sociodemographic educational intervention had a threefold risk ofbeing a case as compared to those who receivedcharacteristics associated with increased risk of

lower limb complications were male gender [odds health information regularly. The study identifiesfactors most likely to be related to adverseratio (OR) 5 2.5, confidence interval (CI) 1.6–3.9],

age between 50 and 70 years as opposed to outcome and permits to discriminate betweenavoidable and unavoidable factors. ( Journal ofyounger than 50 (OR 5 3.6, CI 2.1–6.3) and being

single as opposed to married (OR 5 1.4, CI 1.1–1.8). Diabetes and Its Complications 12;1:10–17,1998.) 1998 Elsevier Science Inc.Among clinical variables, treatment with insulin

for IDDM and NIDDM patients was an important

INTRODUCTIONMedical Statistics and Clinical Epidemiology Department (M.E-S.,

M.A-F.), Medical Research Institute, Alexandria University, Alexan- Aconsiderable amount of disability in diabet-dria, Egypt; Department of Clinical Pharmacology and Epidemiol- ics is caused by the peculiar susceptibilityogy (N.S., F.C., D.C., G.T., A.N.), Istituto Di Ricerche Farracolo Giche

of lower extremities to severe tissue dam-Mario Negri, Consorzio Mario Negri Sud, 66030 S. Maria ImbaroChieti; Institute of Internal Medicine (M.M.B.), Endocrine and Meta- age. The combination of chronic foot ulcer-bolic Science, University of Perugia, Perugia; Ospedale di Pescara ation, sepsis, and gangrene is the chief cause of pro-(F.C.), Centro di Diabetologia, Universita di Chieti, Chieti; Ospedale longed hospitalization for diabetic patients and accountsMolinette, (Q.C.), Centro di Diabetologia, Torino; Ospedale Carda-relli (E.M.D.F.), XI Divisione di Medicina Interna e Diabetologia, ; for more than one-half of the nontraumatic amputa-and Ospedale Civile (C.T.), Servizio di Diabetologia, Udine, Italy tions performed in some developed countries.1–3 The

Reprint requests to be sent to: Dr. Antonio Nicolucci, Department age-adjusted risk for lower extremity amputation hasof Clinical Pharmacology and Epidemiology, Consorzio Mario NegriSud, 66030 S. Maria Imbaro, Chieti, Italy. been reported to be 15 times greater in diabetics than

Journal of Diabetes and Its Complications 12:10–17 1998 Elsevier Science Inc. All rights reserved. 1056-8727/98/$19.00655 Avenue of the Americas, New York, NY 10010 PII S1056-8727(97)00001-9

J Diab Comp 1998; 12:10–17 DIABETIC COMPLICATIONS OF LOWER LIMB 11

in nondiabetics.4 The major factors contributing to To obtain a substantial reduction of diabetic lowerextremity complications, it is thus necessary to identifydamage of the diabetic foot are neuropathy, arterial

atherosclerosis, and bacterial infection.5 Routine physi- the factors that are most relevant in defining the riskprofile of diabetic patients, particularly those factorscal examination may reveal clues leading to the diagno-

sis of neuropathy.6 that can be considered avoidable because they are re-lated to patients’ and doctors’ practices and attitudes.Generally, development of diabetic complications is

strictly related to metabolic control which is deter-METHODSmined by a variety of factors.7,8 Diabetic lower limb com-

plications, in turn, may be influenced by a number The study was carried out between December 1993of factors, including those related to the interaction and June 1994 in 17 of 20 Italian regions. It was a case-between patients and the health-care system. Problems control study15 in which patients were identified in 35related to accessibility of care, the patients’ satisfaction, diabetes outpatient clinics (DOCs) and 49 general prac-or co-ordination between the various health profes- titioners’ offices (GPs). All Italian citizens are healthsionals involved in the care of diabetic patients can insured and registered with a general practitioner. Onhave a major impact on the acceptability of medical average, 15–45 diabetic patients are registered by eachrecommendations.9–11 Equally important in determin- GP. Clinical records for all registered diabetic patientsing good compliance and adequate self-care are factors were available both in DOCs and GPs, and tracing ofsuch as age, co-morbidity, socio-economic status, and patient follow-up visits was possible.social support.12,13

Patients with insulin-dependent diabetes mellitusStarting from these premises, representatives of vari- (IDDM) or non–insulin-dependent diabetes mellitus

ous government health departments and patients’ organ- (NIDDM) with a duration of at least 5 years were in-izations met with diabetes experts under the aegis of cluded in the study as cases if they had foot ulcer,the Regional Office of the World Health Organization claudication, gangrene and/or ischemic rest pain lasting(WHO) and the International Diabetes Federation, in 15 days or more, by-pass or angioplasty for peripheralSaint Vincent, Italy, in October 1989. As a result of the vasculopathy, or if they had undergone amputationmeeting, 5-year targets were defined, directed primar- within the previous 12 months. In DOCs, all diabeticily to the reduction of major diabetic complications.14

patients eligible as cases were identified among sub-jects seen during the study period. All eligible cases

1 The Italian Study Group for the Implementation of the St. Vincent in the charge of GPs were enrolled. Patients were con-Declaration included Co-ordinator: M. Massi Benedetti; Scientific Com- sidered eligible as controls if they had IDDM ormittee: F. Capani, Q. Carta, M.E. De Feo, C. Taboga, G. Tognoni; Co-ordinating Center: A. Nicolucci, D. Cavaliere, M. Abdel-Fattah, N. NIDDM with a duration of at least 5 years and if theyScorpiglione, M. Belfiglio, F. Carinci, M. El-Shazly, D. Labbrozzi, E. had never been affected by any of the aforementionedMari, G. Angeli, M. Olivieri. The Participating clinicians included complications of the lower limb. In general prac-Diabetes Clinics: S. Ponzano (Alessandria); P. Fumelli, P. Sorichetti(Ancona); G.M. Nardelli, A. D’Alessandro (Bari); F. Farci (Cagliari); titioner’s offices, all eligible patients were enrolled asA. Aiello, M.R. Cristofaro (Campobasso); M. Padula, E. Simeone controls. After exclusion of patients who did not fulfil(Casoli); R. Biagioli, C. Santini (Cesena); V. Rotolo, P.M. Miniussi eligibility criteria, three controls for each case were(Cividale del Friuli); A. Berton, C. Ruffino (Finale Ligure); S. Pocciati(Foligno); C. Bordone (Genova); M. Tagliaferri, C. Vitale (Larino); enrolled. Because of the large number of patients inG. Brusco, E. Caruso (Lauria); A. Venezia (Matera); M.E. De Feo, P. the care of DOCs, a random sample was recruited asGuerriero, G. Corigliano, D. Vitale (Napoli); M. Trovati, C. Ponziani control from among eligible patients in such a way(Orbassano); E. Secchi (Ozieri); E. Savagnone (Palermo); C. Coscelli(Parma); M. Massi Benedetti, R. Norgiolini (Perugia); F. Capani, G. that the case/control ratio was the same as that GPs.La Penna (Pescara); D. Giorgi Pierfranceschi (Piacenza); R. Anichini This permitted to avoid any imbalance in the selection(Pistoia); G. Monesi, E. Cecchetto (Rovigo); S. De Cosmo, S. Bacci

of cases and controls from the two different sources(S. Giovanni Rotondo); G. Pipicelli, A. Mosca (Soverato); S. Albano,C. Spinelli (Taranto); Q. Carta, G. Petraroli, M. Porta, M. Tomalino that could have affected the risk estimate.(Torino); C. Taboga (Udine), G. Erle and L. Lora (Vicenza). GeneralPractitioners: M. Cappelletti (Alessandria); R. Giaretta (Altavilla Vi- Measurements. All patients enrolled in the study ascentina); E. Mossuto (Arqua Polesine); A. Spina (Avellino); V. D’Ales- cases or controls received a 45 min interview by pre-sandro (Bari); F. Richeri (Caice Ligure); L. Pascali (Camerano); L.

viously trained physicians. Clinical data were obtainedPuddu (Cagliari); G. Ragazzi (Camisano); M. Rusco (Cardito); V.Biagini, I. Garavina (Cesena); F. Magini, C. Polidori (Citta di by reviewing medical records. Questions focused uponCastello); S. Previato (Crespino); G.M. Masazza (Finale Ligure); L. exposures of interest including sociodemographic (age,Tomain (Fontecchio); A. Bragiotto (Frassinelle); M. Lioniello (Frat-

gender, marital status, education, and occupation),taminore); G. Di Menza (Fubine); E. Mazzoccato (Isola Vicentina);F. Gesualdi (Latronico); G. Capozza, F. Morelli, R. Tataranni clinical (type and duration of diabetes, co-morbidity(Matera); E. Saffi Guistini (Montale); E. Magliani, G. Sampaolo and presence of other diabetic complications), personal(Osimo); L. Galvano, L. Spicola (Palermo); E. Goracci, S. Sbrenna

(smoking and alcohol consumption), and health-care(Perugia); G. Meucci (Pistoia); S. Porru (Quartu S. Elena); A. Briganti,C.A. Belli (Recco); A. Benedetto, S. Burzacca (Rivalta di Torino); E. characteristics (accessibility, self-care, social support,De Bella, A. Di Carluccio, E. Fantini, P. Pietravalle, M. Turato (Roma); frequency of educational interventions received). ToS. Mella, F. Paparella (Rovigo); M. Bertone, M. Zoppi (Torino); G.Cabri (Vicenza); and E. Maragnano (Villadose). enhance uniformity and precision of measuring meth-

12 EL-SHAZLY ET AL. J Diab Comp 1998; 12:10–17

ods, especially for data relying upon clinical judgment, effect of the variables, a multiple logistic regressionwas utilized for the final analysis, with backward selec-all the participating physicians were trained in data

collection, and questionnaire clarity and acceptability tion of the variables to be included in the final model.17

Both in univariate and multivariate analysis, the associ-were verified by interviewing a small number of pa-tients. The data collected referred to the patients’ clini- ation between exposures and outcome is thus ex-

pressed in terms of odds ratios (OR) together with theircal situation at the time of the interview. We also col-lected information on accessibility of health services 95% confidence intervals (95% CI).

All the explanatory variables included in the logisticand health habits relative to the previous 5 years, aperiod of time presumably antecedent to the develop- model were categorized into two or more levels, (RC 5

reference category): Age: younger than 50 years (RC),ment of lower limb complications, to test the effect ofthese variables as exposure factors. 50–70 years, older than 70; Gender: females (RC), males;

Marital status: married (RC), single, divorced/wid-Patients were classified as having IDDM if their ageat diagnosis was under 30 years and insulin was used owed; Education: high (RC), intermediate, elementary,

illiterate; Occupation: professional/managerial (RC),continuously from the time of diagnosis. Patients wereconsidered as NIDDM if their age at diagnosis was technical/clerical, skilled workers/artisan, unskilled

worker, others; Type of diabetes: NIDDM (RC), IDDM,over 30 years with no evidence of ketonuria. Hyperten-sion was considered uncontrolled by treatment on the NIDDM-insulin treated; Duration of diabetes in years:

less than 10 years (RC), 10–20 years, more than 20; Gly-basis of clinical judgment, and confirmed by the pres-ence of blood pressure values exceeding 160/90 mm cated hemoglobin level: within normal range (RC), ab-

normal; Co-morbidity: no (RC), one controlled, two con-Hg on the patient’s records. Similarly, patients wereclassified as having diabetic neuropathy on the basis of trolled, more than two or any uncontrolled; Cardio or

cerebrovascular disease: no (RC), yes; Diabetic neurop-the presence of clinical symptoms and signs. Glycatedhemoglobin levels referred to the last values in the athy: no (RC), yes; Eye complications: no (RC), yes;

Diabetic nephropathy: no (RC), yes; Accessibility to theprevious 12 months. Since normal ranges for glycatedhemoglobin varied in different centers, the percentage health-care facility: alone (RC), with help; Self-manage-change with respect to the upper normal value was ment of insulin therapy: yes (RC), no; Self-monitoringutilized (actual value/upper normal limit 3 100). Levels of glycemia: yes (RC), no; Regular follow-up visits: yesexceeding 30% of the upper normal value were consid- (RC), no; Regularity of diet: yes (RC), no; Frequencyered abnormal. Patients were considered as nephro- of educational interventions: regular (RC), occasional,patic if they underwent dialysis or had serum creati- never; Smoking: nonsmoker (RC), current, ex-smokernine level of 3 mg/dL or more. Co-morbidity included 5 years or less, ex-smoker more than 5 years; Alcoholconditions that had already been present previous to consumption: no (RC), 1–4 cups/day, more than 4the diagnosis of the complication (angina pectoris, hy- cups/day. Since we had no a priori hypothesis regard-pertension, renal disease, endocrine dysfunction, dis- ing possible interactions among the aforementionedlipidemia, and liver diseases). In the classification ac- variables, and to avoid overfitting of the logistic model,cording to employment status, considered as a proxy no interaction term was included in the analysis.for socio-economic status, husband’s employment was

RESULTSconsidered for housewives, whereas the last employ-ment status was considered for retired patients. Infor- A total of 348 diabetic cases with major complicationsmation on the compliance with visit scheduling and with of the lower extremities and 1050 diabetic patients withdietary recommendations was based on the physician’s no complications of the lower extremities were re-judgment. cruited. The sociodemographic, clinical, and care-

related characteristics, together with the results of theSample Size Estimation. Assuming that a hypotheti-univariate analyses are reported in Tables 1–3.cal factor has a prevalence of 10% in the control popula-

The results of the logistic regression analysis aretion and is associated with a relative risk of developingsummarised in Table 4 and described below.complications of two or more, the number of cases

required is 329, (with a 5 0.05 and 12b 5 0.95) assum- Sociodemographic Characteristics. Male patientsing a case/control ratio of 1:3.16 The actual sample of had a higher risk of developing lower extremity com-348 cases thus allows for a reliable detection of risk plications as opposed to female patients (OR 5 2.5, CIfactors with a lower prevalence in the control group 1.6–3.9), while patients aged 50–70 years showed aor those presenting a weaker association with the out- higher probability of being a case compared to thosecome of interest. younger than fifty (OR 5 3.6, CI 2.1–6.3). Regarding

civil status, single patients were more liable to developStatistical Analysis. Analysis was initially carried outa lower limb complication than married ones (OR 5based on a series of univariate comparisons. In order

to control simultaneously for the possible confounding 1.4, CI 1.1–1.8). No significant association could be


TABLE 1. SOCIODEMOGRAPHIC CHARACTERISTICS OF CASES (N 5 348) AND CONTROLS (N 5 1050)

Lower Limb Complications

Cases Controls

No. (%) No. (%) OR (95% CI)

Age,50 years (RC) 18 (5.2) 138 (13.1) 1.050–70 years 155 (44.5) 514 (49.0) 2.3 (1.3–4.0).70 years 175 (50.3) 398 (37.9) 3.4 (2.0–5.9)

GenderFemale (RC) 128 (36.8) 560 (53.3) 1.0Male 220 (63.2) 490 (46.7) 2.0 (1.5–2.5)

Marital statusMarried (RC) 232 (66.7) 712 (67.8) 1.0Single 39 (11.2) 113 (10.8) 1.1 (0.7–1.6)Divorced/widowed 77 (22.1) 225 (21.4) 1.1 (0.8–1.4)

EducationHigh (RC) 54 (15.5) 182 (17.3) 1.0Intermediate 60 (17.2) 208 (19.8) 1.0 (0.6–1.5)Elementary 214 (61.5) 620 (59.0) 1.2 (0.8–1.7)Illiterate 20 (5.7) 40 (3.8) 1.7 (0.9–3.3)

OccupationProfessional/managerial (RC) 8 (2.3) 57 (5.4) 1.0Technical/clerical 53 (15.2) 180 (17.1) 2.1 (0.9–5.1)Skilled worker/artisan 86 (24.7) 184 (17.5) 3.3 (1.5–7.9)Unskilled worker 152 (43.7) 428 (40.8) 2.5 (1.1–5.9)Others 49 (14.1) 201 (19.1) 1.7 (0.7–4.2)

RC, reference category; OR, odds ratio; CI, confidence interval.

detected between development of complications and education, patients who had never received any kindof health education showed a more than threefoldlevel of education or employment status.probability of being a case as opposed to patients who

Clinical Variables. Type of diabetes was associated regularly received educational information (OR 5 3.1,with the outcome of interest. Patients with IDDM (OR 5 CI 1.3–89). Smoking and alcohol consumption were3.9, CI 1.4–10.7) and those with NIDDM-insulin treated not independently related to the outcome of interest.(OR 5 1.4, CI 1.1–2.8) had an increased risk of compli-cation as compared to NIDDM patients. Diabetic neu- DISCUSSIONropathy was strongly and positively related to lower To our knowledge, this is one of the largest case-controllimb complications (OR 5 3.0, CI 2.1–4.2). The presence studies conducted to identify the risk factors for theof cardiac or cerebrovascular diseases was also signifi- development of the most important diabetic complica-cantly associated with an increased complication risk tions of the lower extremities. The focus on the problem(OR 5 1.5, CI 1.2–1.8). Patients showing poor metabolic of avoidability, and thus on quality-of-care-related is-control had a 20% higher risk (OR 5 1.2, CI 1.1–1.4). sues required the involvement of a large number ofThe presence of diabetic retinopathy, nephropathy, or patients, reflecting different settings and practice styles.hypertension, as well as co-morbid conditions was not Furthermore, patients were enrolled from almost allindependently associated with the outcome. Similarly, of the Italian regions, thus making the results morediabetes duration was not found to be independently generalizable.related to the outcome. Our data show that several factors related to patient

characteristics, clinical variables, and delivery of care,Health-Care Related Variables and Patient Practice.Patients who needed help in reaching the health-care play an important role in the development of diabetic

complications of the lower limb. Among patient fac-facility before the development of the complicationshowed an almost 50% higher risk than those who did tors, gender and age between 50 and 70 years were

important predictors. The magnitude of risk could notnot need help (OR 5 1.4, CI 1.1–2.2), while those whodid not attend follow-up visits regularly were at twice be significantly determined for those over 70 years of

age probably because of the higher mortality rate inthe risk (OR 5 2.0, CI 1.3–3). Regarding diabetic health


TABLE 2. CLINICAL CHARACTERISTICS OF CASES (N 5 348) AND CONTROLS (N 5 1050)


Cases Controls

No. (%) No. (%) OR (95% CI)

Type of diabetesNIDDM (RC) 94 (27.0) 563 (53.6) 1.0IDDM 45 (12.9) 155 (14.8) 1.7 (1.2–2.6)NIDDM-IT1 209 (60.1) 332 (31.6) 3.8 (2.8–5.0)

Duration of diabetes,10 years (RC) 69 (19.8) 329 (31.3) 1.010–20 years 141 (40.5) 441 (42.0) 1.5 (1.1–2.1).20 years 138 (39.7) 280 (26.7) 2.4 (1.7–3.3)

Glycated hemoglobina

Within normal range (RC) 119 (43.9) 480 (56.6) 1.0Abnormal 152 (56.1) 368 (43.4) 1.7 (1.3–2.2)

Co-morbidityNo (RC) 144 (41.4) 497 (47.3) 1.0One controlled 114 (32.8) 316 (30.1) 1.3 (0.9–1.7)Two controlled 39 (11.2) 110 (10.5) 1.2 (0.8–1.9).Two controlled or any

uncontrolled 51 (14.7) 127 (12.1) 1.4 (0.9–2.1)Hypertension

No (RC) 180 (51.7) 571 (54.4) 1.0Yes controlled 130 (37.4) 377 (35.9) 1.1 (0.8–1.4)Yes uncontrolled 38 (10.9) 102 (9.7) 1.2 (0.8–1.8)

C/V diseasesNo (RC) 262 (75.3) 933 (88.9) 1.0Yes 86 (24.7) 117 (11.1) 2.6 (1.9–3.6)

Diabetic neuropathyNo (RC) 199 (57.2) 843 (80.3) 1.0Yes 149 (42.8) 207 (19.7) 3.1 (2.3–4.0)

Diabetic retinopathyNo (RC) 176 (50.6) 688 (65.5) 1.0Yes 172 (49.4) 362 (34.5) 1.7 (1.4–2.4)

Diabetic nephropathyNo (RC) 310 (89.1) 975 (92.9) 1.0Yes 38 (10.9) 75 (7.1) 1.6 (1.0–2.5)

RC, reference category; OR, odds ratio; CI, confidence interval; NIDDM, non–insulin-dependent diabetes mellitus; IDDM, insulin-dependent diabetesmellitus; IT, insulin treated; C/V, cardio- or cerebrovascular disease.

a Data were not available for 76 cases and 203 controls.

this age category, thus demonstrating an apparent lower strong predictor of the outcome, while clinical durationwas not a statistically significant predictor for the de-risk in this group of patients.

Socio-economic status, as defined by occupation and velopment of complications. The same finding was men-tioned in a previous report,20 in contrast to what hadeducation was not associated with the outcome. Be-

cause of the possible correlation between employment been reported by others;21 nevertheless, when we ranthe model without age, the duration of diabetes enteredand years of education, we also ran a logistic model

excluding employment status. In this case as well, edu- the logistic model, thus indicating a correlation be-tween these two variables.cation did not prove to be an independent predictor.

We found that the absence of family support (single Hypertension was not a risk factor for diabetic com-plications of lower extremities in our study, in agree-patients) was significantly associated with the develop-

ment of complications, confirming other reports that ment with reports from other case-control studies.20,22

Also, no consistent agreement on hypertension as asuggest the importance of family support in the man-agement of chronic diseases.18,19 significant predictor variable was obtained from recent

prospective studies on lower extremity amputation inAmong the clinical variables, type of diabetes was a


TABLE 3. PATTERNS OF CARE AND PATIENTS’ HABITS FOR CASES AND CONTROLS


Cases Controls

No. (%) No. (%) OR (95% CI)

Need of help to reach health care facilityNo (RC) 239 (68.7) 802 (76.4) 1.0Yes 109 (31.3) 248 (23.6) 1.5 (1.1–1.9)

Ability to adjust insulin dosea

Yes (RC) 79 (32.8) 235 (49.2) 1.0No 162 (76.2) 243 (50.8) 2.0 (1.4–2.8)

SMBGYes (RC) 209 (60.1) 679 (64.7) 1.0No 139 (39.9) 371 (35.3) 1.2 (0.9–1.6)

Regular follow-up visitsYes (RC) 234 (67.2) 856 (81.5) 1.0No 114 (32.8) 194 (18.5) 2.2 (1.6–2.8)

Compliance with dietary recommendationsYes (RC) 208 (40.2) 709 (32.5) 1.0No 140 (59.8) 341 (67.5) 1.4 (1.1–1.8)

Frequency of educational interventionRegular (RC) 76 (21.8) 307 (29.2) 1.0Occasional 263 (75.6) 732 (69.8) 1.5 (1.1–2.0)Never 9 (2.6) 11 (1.0) 3.3 (1.2–9.0)

SmokingNo (RC) 172 (49.5) 663 (63.1) 1.0Current 54 (15.5) 170 (16.2) 1.2 (0.9–1.8)Ex ,5 years 45 (12.9) 65 (6.2) 2.7 (1.7–4.1)Ex >5 years 77 (22.1) 150 (14.5) 2.0 (1.3–3.0)

Alcohol consumptionNo (RC) 155 (44.6) 542 (51.6) 1.01–4 cups/day 140 (40.2) 408 (38.9) 1.2 (0.9–1.6).4 cups/day 53 (15.2) 100 (9.5) 1.9 (1.3–2.8)

RC, reference category; OR, odds ratio; CI, confidence interval; SMBG, self-monitoring of glycemia; Ex, ex-smoker; IDDM, insulin-dependent diabetesmellitus; NIDDM, non–insulin-dependent diabetes mellitus; IT, insulin treated.

a Only for patients on insulin treatment (IDDM and NIDDM-IT).

diabetic patients.20,21,23–25 In contrast, the presence of els of glycated hemoglobin could have a poor correla-tion with the metabolic control before the complicationmacrovascular involvement, indicated by a past his-

tory of cardiac or cerebrovascular disease was noticed developed. This excess risk related to increased levelsof glycated hemoglobin may be meaningful becauseto be related to the development of lower limb compli-

cations. Among the other diabetes complications, pe- many of the complications of diabetes may result indi-rectly from chronic hyperglycemia.20,26ripheral neuropathy emerged as a major independent

risk factor for the outcome. This finding is quite consis- Although no significant association emerged withinadequate compliance to dietary recommendations,tent with other case-control20,22 and prospective 21,23–25

studies that also demonstrated a close association be- poor compliance with visit scheduling was associatedwith an increased risk of being a case. This reflects thetween amputation and other microvascular complica-

tions of diabetes. Nevertheless, no significant associa- importance of the effects of physician-patient interac-tion on the outcomes of chronic diseases,9 and empha-tion with diabetic eye or renal complications could be

detected in our study. The role of metabolic control as sizes the role of continuity in diabetes care. This con-cept is further reinforced when considering the resultsindicated by the level of glycated hemoglobin emerged

as a significant predictor variable for this type of dia- relative to diabetes education. Those patients whonever received information on specific aspects of diabe-betic complication, although the association was weak.

While we decided to include metabolic control among tes care (self-management, diet, regular foot inspection,physical activity, etc.) showed a strikingly increasedthe covariates, it should be emphasized that, because

of the retrospective nature of the study, the actual lev- risk of major complications of the lower extremities.


TABLE 4. RESULTS OF MULTIVARIATE extremity complications has already been reported inLOGISTIC REGRESSION ANALYSIS many studies on diabetic patients.20,21,23,28

As a final point, some possible limitations of ourCovariate OR 95% CIstudy need to be discussed. As in any case-control study,

Age its design is by definition retrospective. It is, thus, im-,50 years (RC) 1.0 possible to draw any conclusion about the causal rela-50–70 years 3.6 (2.1–6.3) tionship between the variables investigated and the.70 years 0.8 (0.6–1.0) outcome of interest. Nevertheless, this limitation is bal-Gender

anced by the possibility of rapidly monitoring the clini-Female (RC) 1.0cal practice, identifying avoidable risk factors in largeMale 2.5 (1.6–3.9)populations, and setting priorities for preventive strat-Marital statusegies. Also, our findings are consistent with those emerg-Married (RC) 1.0

Single 1.4 (1.1–1.8) ing from prospective studies.Divorced/widowed 0.7 (0.5–1.0) The presence of the complications could be responsi-

Type of diabetes ble for recall bias regarding the kind of education re-NIDDM (RC) 1.0 ceived. In other words, patients suffering from theIDDM 3.9 (1.4–10.7) complication could be more prone to deny having hadNIDDM-IT 1.4 (1.1–2.8) adequate diabetic care information. Nevertheless, theCardio- or cerebrovascular

results are very consistent with those coming fromdiseaserandomized clinical trails, showing the efficacy of edu-No (RC) 1.0cational interventions.Yes 1.4 (1.2–1.8)

Another possible limitation of the case-control de-Diabetic neuropathyNo (RC) 1.0 sign depends on the correct choice of the control group.Yes 3.0 (2.1–4.2) In our study the control group was randomly selected

Glycated hemoglobin from a very large population, reflecting different set-Within normal range (RC) 1.0 tings of care and practice styles; thus, it likely repre-Abnormal 1.2 (1.1–1.4) sents a realistic picture of the true prevalence of the

Need of help to reach the investigated risk factors in the general population.health care facilityNo (RC) 1.0 CONCLUSIONYes 1.5 (1.1–2.2)

Regular follow-up visits This work has been undertaken in the framework ofYes (RC) 1.0 the initiatives for the implementation in Italy of the rec-No 2.0 (1.3–3.0) ommendations of the Saint Vincent Declaration, aimed

Frequency of educational at achieving a substantial reduction in the rate of majorintervention diabetic complications.

Regular (RC) 1.0 The study identifies the factors most likely to be relatedOccasional 1.2 (0.8–1.3)to adverse outcome and permits to discriminate betweenNever 3.1 (1.3–8.9)avoidable and unavoidable factors. Among the former,

RC, reference category; OR, odds ratio; CI, confidence interval; IDDM, adequate educational intervention seems to be theinsulin-dependent diabetes mellitus; NIDDM, non–insulin-dependent dia- most effective tool for reducing the incidence of com-betes mellitus; IT, insulin treated.

plications of the lower extremities in diabetic patientswith intensive emphasis on the importance of regularfollow-up visits and continuous care. The study alsoOur finding supports the results of two other recentunderlines the need for setting priorities and tailoringreports that describe the benefit of patient educationspecific interventions to those patients who, on thein decreased amputation rates among diabetics.20,27

basis of their characteristics (male gender, older age,As far as life-style is concerned, no association couldinsulin treated, low level of autonomy), are more likelybe detected either with smoking or with drinking habits.to develop a diabetic complication of lower extremities.The quantitive aspect of smoking showed no addi-

tional significant results. Data on the relation of ciga- ACKNOWLEDGMENTrette smoking to lower limb complications are inconsis-

This study was supported by Pfizer Italiana S.p.A. and bytent. Although cigarette smoking is a strong risk factorthe Italian National Research Council (CNR, Rome) contractfor peripheral vascular disease in both diabetic and no. 94.00989.04. We thank Consorzio di Medicina Tropicale

nondiabetic patients, it does not appear to contribute (CMT), Italy for granting fellowships to Drs. Abdel-Fattahsubstantially to the excess risk of amputation in diabe- and El-Shazly. We also thank Maria Pia De Simone for revi-

sion of English text.tes.25 The lack of association between smoking and lower


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