Frequencies of each of the metabolic syndrome components, adjusted for age, sex, educational level, and family history of diabetes, are shown for the 4 glycemic status groups in Table 4. The most prevalent component in all groups was elevated blood pressure, followed by elevated waist circumference. A progressive increase of frequency in all components according to glycemic status was observed, such that the lowest frequency was observed in the normoglycemia group, followed by isolated HbA1c group, isolated FPG group, and the highest in the both criteria group. The frequency of the metabolic syndrome as a whole was 15.0% in patients with normoglycemia, 59.5% in patients with isolated HbA1c criterion, 62.0% in patients with isolated FPG criterion, and 76.2% in patients with both criteria of prediabetes. Because of the low prevalence in normoglycemic patients with respect to the other groups, the trend in the magnitude of the prevalence over the 4 groups was deviated from linearity.
The distribution of the number of components present—excluding elevated glycemia component—for each glycemic status group is showed in the Figure 1. It can be seen that the percentage of individuals with either 0 or 1 component is greater in the normoglycemia group, whereas the percentage of individuals with 2, 3, or 4 components is greater in the group with both criteria of prediabetes. The percentages of patients who did not meet any component of metabolic syndrome were 21% in individuals with normoglycemia, 11% in those with isolated HbA1c criterion, 8% in those with isolated FPG criterion, and 5% in those with both criteria. On the other end of the distribution, patients who meet 4 components, the percentages were 3%, 7%, 7%, and 11%, respectively.
Individuals with prediabetes defined by both HbA1c and FPG criteria had the worst values in clinical and biochemical characteristics related to increase cardiovascular risk, and the highest frequency of metabolic syndrome. On the other hand, individuals with prediabetes defined by only one—HbA1c or FPG—criterion were at an intermediate cardiometabolic risk profile, showing a more favorable profile than individuals with 2 criteria, but less favorable than individuals without any criteria of prediabetes.
Results of comparisons of the 4 glycemic status groups show that there are differences among groups in some of characteristics examined. It is worth mentioning, differences in sex distribution observed in prediabetic groups, where the proportion of men was greater in the isolated FPG group and the proportion of women was greater in the isolated HbA1c group. Similar finding can be observed in other studies with prediabetic groups defined by HbA1c and FPG criteria.19,20 Also, Lipska et al21 have been pointed that women were more likely to be identified with dysglycemia by HbA1c than FPG.
Studies comparing cardiometabolic risk measures in prediabetes groups defined by FPG and IGT criteria have also found in categories with any isolated criterion, an intermediate risk profile between normoglycemic status—low risk—and the combination of 2 criteria of prediabetes—high risk.10,11 Moreover, other studies based on nondiabetic individuals, which have considered HbA1c and FPG as prediabetes criteria, had observed higher levels of some cardiovascular risk factors in individuals with prediabetes by both criteria.19,20 By contrast, no differences in cardiometabolic risk profiles were observed by Marini et al14 when they compared 3 groups of individuals with prediabetes based on the same criteria. The fact that having at least 1 cardiometabolic risk factor was a criterion to include participants in their study could explain this inconsistency, because their study groups were more homogeneous respect to baseline risk.
There is sufficient evidence that metabolic syndrome is strongly related with hyperglycemia.4,5,22 As expected, we found a high percentage of metabolic syndrome in individuals with prediabetes. A higher prevalence of this syndrome in individuals with both criteria of prediabetes than in those with only one criterion has been reported.5,10 In our study, apart from the frequency of metabolic syndrome as a whole, the percentage of individuals in normoglycemia group who had no metabolic syndrome components present was 4 times higher than the corresponding percentage in both criteria group. While the percentage of individuals in normoglycemia group who met the 4 metabolic syndrome components was less (approximately half) than the corresponding percentage of individuals in isolated criterion groups, and even less (approximately one-third) compared with the same in the both criteria group. This is consistent with the other findings of this study, the cardiometabolic risk increases according to the number of prediabetes criteria present increases.
The worst risk profile observed in individuals with both criteria of prediabetes could be explained by the differences in the role of FPG or HbA1c to detect glucose metabolism disorders. If each measure represents a different pathophysiologic mechanism, it can be expected that individuals with both criteria of prediabetes have a higher risk than those with only one criterion.
Compared with individuals in the isolated FPG group, it is noteworthy that those in the isolated HbA1c group had slightly lower values in the most of clinical and biochemical parameters related to cardiovascular risk. In this sense, Heianza et al20 have pointed a similar finding: individuals diagnosed by isolated HbA1c criterion were more likely to have lower values in body mass index, blood pressure, and serum concentrations of triglyceride, HDL cholesterol, uric acid, and gamma glutamyltransferase. The above results could be indicative of a lower cardiovascular risk profile in individuals with isolated HbA1c criterion at diagnosis of prediabetes. We, however, must not overlook that more favorable waist circumference and HDL cholesterol values were observed in the isolated FPG group. Moreover, there are discrepancies in findings across studies. For example, Saukkoken et al23 reported higher mean values of body mass index and triglycerides in the isolated HbA1c group compared with isolated FPG group, and not differences in blood pressure and waist circumference between both groups. And other authors have also reported contradictory results, for some parameters slightly lower values were observed in HbA1c group, and for others in FPG group.14,19
In a recent study conducted in middle-aged Caucasian-Europeans, it can be observed that the subjects classified as prediabetic using HbA1c criterion has lower body mass index, waist circumference, and triglycerides levels and higher HDL cholesterol than those subjects classified using FPG criterion.24 In this study, when we analyzed waist circumference and HDL cholesterol parameters using metabolic syndrome components cut points, we also observed that frequencies of these criteria were lower in isolated HbA1c group than isolated FPG group. The same has been seen for elevated triglycerides and elevated blood pressure criteria, and metabolic syndrome as a whole. This finding is consistent with those studies on prevalence of metabolic syndrome comparing HbA1c criterion of elevated glycemia with FPG criterion, where the prevalence was lower when alone HbA1c criterion was considered to determine the presence of syndrome.25–27 However, in the only one study that shows results of metabolic syndrome components, the frequencies of elevated waist circumference and reduced HDL cholesterol were higher in the group based on HbA1c criterion than in the group based on FPG.25 On the other hand, higher FPG levels rather than higher HbA1c levels have been more strongly associated with an increased risk for development of hypertension at 5 years among Japanese.28
Then, several hypotheses can be proposed about the presence of isolated HbA1c criterion at prediabetes diagnosis. First of all, it identifies individuals with a slightly lower metabolic risk status compared with those detected by isolated FPG criterion. Second, it identifies individuals with a risk status related to a very early stage of cardiovascular disease. And finally, it cannot be ruled out that isolated HbA1c criterion is more specific to identify those characteristics, which are more strongly related to cardiovascular diseases, such as low HDL cholesterol and high waist circumference.
This study is being carried out in routine clinical practice and includes a large number of individuals across nationwide, which are being followed annually. Despite this strength, all patients studied are primary health care users, and the frequency of cardiometabolic risk factors could be different from other settings or from the general population. So care should be taken in generalizing these results.
This study had some limitations. First, patients were classified into groups based on single measurements of HbA1c and FPG, and so we cannot rule out the possibility of misclassification bias because of potential problems with intraindividual variability of glycemia measures.29 Second, a level of HbA1c ≥ 5.7% was considered as an additional criterion of elevated glycemia component of metabolic syndrome, which is not included in current definitions of this syndrome. We, however, calculated the frequencies of metabolic syndrome excluding the elevated glycemia component (data not shown) and the results were very similar to those observed when this component was included. This finding support the use of the HbA1c levels in range of prediabetes as an additional measure to screen glycemic component of metabolic syndrome, an issue that has been pointed by some authors.25,30
In conclusion, individuals with prediabetes have a worse cardiometabolic risk profile than normoglycemic individuals, and those with both criteria of prediabetes have the worst risk profile. These results suggest the need to use both criteria in the clinical practice to identify those individuals with the highest cardiovascular risk in order to offer them special attention with intensive lifestyle intervention programs. Some of our findings suggest that individuals with isolated HbA1c criterion at diagnosis of prediabetes might have a slightly lower cardiometabolic risk than those with isolated FPG criterion, but further studies are needed on this topic.
We thank the Sanofi and Novartis for the financial support of the development of the data collection platform, the meetings of researchers, and the monitoring of information collected at baseline. Sanofi and Novartis had no role in the study design, analysis and interpretation of data, writing of the manuscript, nor the decision to submit the manuscript for publication.
*The other members of the PREDAPS Study group are
M. Alonso (La Eria Health Center, Asturias), B. Álvarez (Andrés Mellado Health Center, Madrid), F. Álvarez (La Calzada 2 Health Center, Asturias), J. C. Álvarez (Eras de Renueva Health Center, León), J. J. Antón (Murcia Centro Health Center, Murcia), O. Armengol (Poblenou Primary Care Team, Barcelona), L. Ávila (Almachar Ambulatory Care Facility, Málaga), C. Babace (Rodríguez Paterna Health Center, La Rioja), L. Barutell (Andrés Mellado Health Center, Madrid), M. J. Bedoya (Hereza Health Center, Madrid), B. Benito (Raval Sud Primary Care Team, Barcelona), B. Bilbeny (Raval Sud Primary Care Team, Barcelona), M. Birules (Poblenou Primary Care Team, Barcelona), C. Blanco (Sada Health Center, Coruña), M. I. Bobé (La Mina Primary Care Team, Barcelona), C. Boente (Porriño Health Center, Pontevedra), A. Borras (Canal Salat Health Center, Islas Baleares), R. Bosch (Girona 2 Primary Care Team, Girona), M.J. Brito (La Matanza de Acentejo Health Center, Santa Cruz de Tenerife), J.J. Cabré (Reus-1 Primary Care Team, Tarragona), F. Carbonell (Mislata Health Center, Valencia), F. Carramiñana (San Roque de Badajoz Health Center, Badajoz), A. Casorrán (Fuente de San Luis Health Center, Valencia), R. Colas (Santoña Health Center, Cantabria), B. Cordero (Sta. María de Benquerencia Health Center, Toledo), X. Cos (Sant Martí de Provençals Primary Care Team, Barcelona), G. Cuatrecasas (Sarrià Primary Care Center, Barcelona), C. De Castro (Sta. María de Benquerencia Health Center, Toledo), M. De la Flor (Ntra. Sra. de Gracia Health Center, Sevilla), C. De la Sen (San Gabriel Ambulatory Care Facility, Alicante), R.M. De Miguel (Pubillas Casas Primary Care Team, Barcelona), A.M. De Santiago (Family & Community Medicine Teaching Unit, Guadalajara), M. Del Castillo (Andrés Mellado Health Center, Madrid), D. Dominguez (General Fanjul Health Center, Madrid), M. C. Durán (Lavadores Health Center, Pontevedra), M. Ferreiro (Huerta del Rey Health Center, Sevilla), J. Gamarra (Medina del Campo Rural Health Center, Valladolid), F. García (Don Benito Este Health Center, Badajoz), L. García-Giralda (Murcia-Centro Health Center, Murcia), M.T. Gijón (Los Yébenes Health Center, Madrid), Á. Gómez (Lasarte Health Center, Guipúzcua), M.C. Gómez (Vélez-Málaga Norte Health Center, Málaga), J. C. González (Girona 3 Primary Care Team, Girona), M. González (Alcantarilla Sangonera Health Center, Murcia), E. Granero (Vista Alegre Health Center, Murcia), A.T. Gutiérrez (El Calero Health Center, Las Palmas), F. Gutiérrez (Bombarda-Monsalud Health Center, Zaragoza), L. Gutiérrez (Beraun Health Center, Guipúzcua), M.A. Gutiérrez (Ávila Sur Oeste Health Center, Ávila), A.M. Hernández (El Calero Health Center, Las Palmas), M. Ibáñez (Vandel Health Center, Madrid), R. Iglesias (Lain Entralgo Health Center, Madrid), D. Igual (Manuel Encinas Health Center, Cáceres), A. Jurado (Salvador Caballero Health Center, Granada), R. Llanes (Villanueva de la Cañada Health Center, Madrid), F. López (Martorell Primary Care Team, Barcelona), R. López (El Carmel Primary Care Team, Barcelona), R. López (Artilleros Health Center, Madrid), A. Lorenzo (Alcalá de Guadaira Health Center, Madrid), C. Losada (Adoratrices Clinical Management Unit, Huelva), R. Macia (Roces Montevil Health Center, Asturias), F. Malo (Ares Health Center, Coruña), J. Mancera (Ciudad Jardín Health Center, Málaga), M.J. Mansilla (Martín de Vargas Health Center, Madrid), M.T. Marín (General Ricardos Health Center, Madrid), J.L. Martín (Salvador Caballero Health Center, Granada), F.J. Martínez (Federica Monseny Health Center, Madrid), M.C. Martínez (Raval Sud Primary Care Team, Barcelona), R. Martínez (Oñati Health Center, Guipúzcua), A. Massana (Raval-Sud Primary Care Team, Barcelona), M. Mata (La Mina Primary Care Team, Barcelona), M.S. Mayayo (Martín de Vargas Health Center, Madrid), J.J. Mediavilla (Burgos Rural Health Center, Burgos), L. Mendo (Cadreita Health Center, Navarra), A. Monzón (Vecindario Health Center, Las Palmas), A. Moreno (San Roque Primary Care Center, Badajoz), X. Mundet (El Carmel Primary Care Team, Barcelona), T. Mur (Terrassa Sud Primary Care Center, Barcelona), E. Navarro (Añaza Health Center, Santa Cruz de Tenerife), J. Navarro (Salvador Pau Health Center, Valencia), P. Nogales (Las Águilas Health Center, Madrid), J.C. Obaya (Chopera Health Center, Madrid), C. Oria (Aizarnazabal-Getaria Health Center, Guipúzcua), F. Javier Ortega (Campos-Lampreana Health Center, Zamora), F. Paniagua (Ciudad Jardín Health Center, Málaga), J.L. Pardo (Orihuela I Health Center, Alicante), F.C. Pérez (Martín de Vargas Health Center, Madrid), P.P. Pérez (Mallen Health Center, Sevilla), N. Piulats (Raval Sud Primary Care Team, Barcelona), R. Plana (Ponteareas Health Center, Pontevedra), N. Porta (Terrassa Sud Primary Care Center, Barcelona), S. Poveda (Jumilla Health Center, Murcia), L. Prieto (Cáceres-La Mejostilla Health Center, Cáceres), R. Pujol (Tremp Primary Care Team, Lérida), S. Reixa (Arrabal Health Center, Zaragoza), J. Ripoll (Fuente de San Luis Health Center, Valencia), A. Rodríguez (Anglès Primary Care Team, Girona), J.J. Rodríguez (Villaviciosa de Odón Health Center, Madrid), M.A. Rollán (Los Yébenes Health Center, Madrid), M.T. Rollán (Hereza Health Center, Madrid), L. Romera (Raval Nord Primary Care Team, Barcelona), P. Roura (Badia del Vallès Primary Care Team, Barcelona), J.F. Rubio (Lasarte Health Center, Guipúzcua), A. Ruiz (Pinto Health Center, Madrid), I. Ruiz (La Torrassa Primary Care Team, Barcelona), M. A. Ruiz (Agost Health Center, Alicante), I. Saenz (Espronceda Health Center, Madrid), J. Sagredo (Los Rosales Health Center, Madrid), A. Salanova (Fuente de San Luis Health Center, Valencia), L.G. Sánchez (Carballeda Health Center, Zamora), M. Sánchez (Vista Alegre Health Center, Murcia), G. Sanz (San José Centro Health Center, Zaragoza), D. Suárez (El Calero Health Center, Las Palmas), E. Tarragó (Bellvitge Primary Care Team, Barcelona), J. Torrecilla (Bombarda-Monsalud Health Center, Zaragoza), J.L. Torres (Rodríguez Paterna Health Center, La Rioja), M. Villaró (Terrassa Sud Primary Care Team, Barcelona).
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