In patients with type 2 diabetes mellitus (DM2), the presence of increased waist circumference and triglycerides is a reflection of increased visceral fat and insulin resistance. However, information about the prevalence and clinical characteristics of the hypertriglyceridemic waist (HTGW) phenotype in patients with DM2 is scarce. The aim of the present study was to analyze the prevalence and characteristics of DM2 patients with HTGW.
MethodsWe analyzed 4214 patients with DM2 in this epidemiological, cross-sectional study conducted in primary care centers across Spain between 2011 and 2012. The HTGW phenotype was defined as increased waist circumference according to the International Diabetes Federation criteria for Europids (≥ 94 cm for men and ≥ 80 cm for women) with the presence of triglyceride levels ≥ 150 mg/dL. We compared the demographic, clinical and analytical variables according to the presence or absence of the HTGW phenotype.
ResultsThirty-five percent of patients presented the HTGW phenotype. Patients with the HTGW phenotype had a higher body mass index (31.14 ± 4.88 vs. 29.2 ± 4.82 kg/m2; p < .001) and glycated hemoglobin levels (7.38 ± 1.2% vs. 7 ± 1.07%; p < .001). The presence of hypertension, peripheral arterial disease, cardiac insufficiency and microvascular complications were higher when compared with patients without the HTGW phenotype. Patients with the HTGW phenotype were less adherent to prescribed diet (69.8 vs. 81%; p < .001), exercise (44.6 vs. 58.2%; p < .001) and presented greater weight increase within the year prior to the study visit (29.4 vs. 22.5%; p < .001).
ConclusionsThe HTGW phenotype is prevalent in the Spanish DM2 population and identifies a subgroup of patients with higher cardiometabolic risk and prevalence of diabetic complications.
En los pacientes con diabetes mellitus tipo 2 (DM2) la presencia de aumento de la circunferencia de la cintura y de los triglicéridos es un reflejo del aumento de la grasa visceral y de la resistencia a la insulina. Sin embargo, es escasa la información acerca de la prevalencia y de las características clínicas del fenotipo de cintura hipertrigliceridémica (CHTG) en pacientes con DM2. El objetivo del presente estudio fue analizar la prevalencia y las características de los pacientes de DM2 con CHTG.
MétodosEn este estudio epidemiológico transversal, llevado a cabo en centros de atención primeria de toda España entre los años 2011 y 2012, analizamos a 4.214 pacientes con DM2. El fenotipo CHTG fue definido como un aumento de la circunferencia de la cintura conforme a los criterios de la Federación Internacional de Diabetes para caucásicos (≥ 94 cm para hombres y ≥ 80 cm para mujeres) acompañado de niveles de triglicéridos ≥ 150 mg/dL. Comparamos las variables demográficas, clínicas y analíticas según la presencia o ausencia del fenotipo CHTG.
ResultadosEl 35% de los pacientes presentaron el fenotipo CHTG. Los pacientes con fenotipo CHTG tenían mayor índice de masa corporal (31,14 ± 4,88 vs. 29,2 ± 4,82 kg/m2; p < 0,001) y hemoglobina glucosilada más alta (7,38±1,2% vs. 7±1,07%; p < 0,001). La presencia de hipertensión, enfermedad arterial periférica, insuficiencia cardíaca y complicaciones microvasculares fueron más frecuentes en los pacientes con fenotipo CHTG que los que no lo tenían. Los pacientes con fenotipo CHTG tenían una menor adherencia a la dieta prescrita (69,8 vs. 81%; p < 0,001), al ejercicio (44,6 vs. 58,2%; p<0,001), y el aumento de peso en el año previo al estudio fue mayor (29,4 vs. 22,5%; p<0,001).
ConclusionesEl fenotipo CHTG es prevalente en la población DM2 española e identifica a un subgrupo de pacientes con un elevado riesgo cardio-metabólico y mayor prevalencia de complicaciones diabéticas.
The hypertriglyceridemic waist (HTGW) phenotype was first described by Lemieux in 20001 in an attempt to create a simple tool for identifying individuals with the atherogenic metabolic triad (elevated insulinemia and apolipoprotein B and small, dense LDL particles).
Since its first definition, many reports have demonstrated the usefulness of HTGW as predictive of cardiovascular disease risk, including the analyses from the EPIC-Norfolk cohort and the Framingham Study.2,3 Moreover, cross-sectional and prospective studies have shown the predictive value of the HTGW phenotype in the incidence of type 2 diabetes mellitus (DM2).4–9
DM2 is a heterogeneous condition with diverse clinical phenotypes10 and therapeutic responses.11 Thus, identifying patient subgroups with specific pathophysiology is important for selecting drugs that can address the underlying pathogenic mechanisms rather than solely reducing blood glucose concentrations.12
In patients with DM2, the presence of increased waist circumference and triglyceride levels indicates the presence of increased visceral fat and insulin resistance and seems to correlate with coronary artery disease.13,14 However, information about the prevalence and clinical characteristics of DM2 patients with the HTGW phenotype is scarce. Therefore, the aim of the present study was to analyze the prevalence and characteristics of DM2 patients with HTGW in a large sample of DM2 patients in Spain.
MethodsThe patients included in this analysis participated in the previously reported Diabcontrol Study.15 Briefly, this was an epidemiological, cross-sectional study conducted in primary care centers across Spain between 2011 and 2012 that included 5382 patients with DM2 undergoing antidiabetic therapy. A total of 1797 investigators from 13 autonomous Spanish communities participated in the study. All patients completed a single clinical visit in which glycated hemoglobin (HbA1c) was measured in capillary blood (A1CNow+).16
For the present analysis, we selected patients with available information concerning waist circumference and triglyceride levels. We defined the HTGW phenotype as increased waist circumference according to the International Diabetes Federation (IDF) criteria for Europids (≥ 94 cm for men and ≥ 80 cm for women)17 with the presence of triglyceride levels ≥ 150 mg/dL. We compared demographic, clinical, and analytical variables according to the presence or absence of the HTGW phenotype. Concomitantly, a more stringent HTGW phenotype was defined according to the American criteria for waist circumference (waist circumference ≥ 102 cm for men and ≥ 88 cm for women) and triglyceride levels > 200 mg/dL.18
Results are expressed as frequencies and percentages for qualitative variables and as mean and standard deviation for quantitative variables. The normality of data distribution was evaluated using the Kolmogorov-Smirnov test. We employed Student’s T-test or Mann–Whitney test to analyze the quantitative variables and chi-squared for the qualitative variables. We performed a logistic regression analysis to analyze the variables associated with the HTGW phenotype and the association between HTGW and diabetes complications. All statistical tests were considered significant at p < .05. Statistical analysis was performed using the SAS statistical package (version 9.3).
The study was approved by the Unitat d’Avaluació, Suport i Prevenció (UASP) of Hospital Clínic in Barcelona and was conducted according to the principles of the Declaration of Helsinki and Good Clinical Practice standards. We obtained written informed consent from all patients before including them in the study.
ResultsA total of 4214 patients with DM2 were included, and there were no differences in terms of age, sex, body mass index (BMI), diabetes duration, fasting plasma glucose, HbA1c, and lipid concentrations between the included and excluded patients (data not shown).
The mean age was 66.7 ± 10.7 years, and 728 patients (53.3%) were men. The mean diabetes duration was 8.9 ± 6.3 years, and the mean HbA1c was 7.3 ± 1.2%. According to the definition of the HTGW phenotype for Europids (waist circumference ≥ 94 cm for men and ≥ 80 cm for women and triglyceride levels ≥ 150 mg/dL), 1475 patients (35%) presented the HTGW phenotype. Thirty-two percent of men and 37.9% of women (p < .001) presented the HTGW phenotype. The clinical characteristics of the patients according to the presence or absence of the HTGW phenotype are shown in Table 1.
Clinical characteristics of patients according to the presence or absence of the HTGW phenotype.
HTGW | Without HTGW | p | |
---|---|---|---|
Age, years | 65.2 ± 10.5 | 67.5 ± 10.7 | < .001 |
Smoking, n (%) | 256 (17.5) | 353 (13) | < .001 |
BMI, kg/m2 | 31.1 ± 4.9 | 29.2 ± 4.8 | < .001a |
Waist, cm | 105.8 ± 11.8 | 99.8 ± 13.6 | < .001 |
Diabetes duration, years | 8.6 ± 5.9 | 9.0 ± 6.5 | .051 |
HbA1c, % | 7.4 ± 1.2 | 7.0 ± 1.1 | < .001a |
Fasting glucose, mg/dL | 151.9 ± 45.9 | 134.9 ± 36.9 | < .001 |
AHT, n (%) | 1190 (80.8) | 1955 (71.6) | < .001a |
Systolic BP (mmHg) | 135.9 ± 14.5 | 132.9 ± 13.8 | < .001 |
Diastolic BP (mmHg) | 79.1 ± 9.6 | 76.3 ± 9.1 | < .001 |
Total cholesterol (mg/dL) | 206.3 ± 42.9 | 183.1 ± 36.3 | < .001a |
HDL-c (mg/dL) | 45.3 ± 11.2 | 51.3 ± 13.0 | < .001a |
LDL-c (mg/dL) | 113.9 ± 40.4 | 107.6 ± 31.4 | < .001a |
Triglycerides (mg/dL) | 226.7 ± 95.8 | 112.2 ± 45.0 | < .001 |
AHT: arterial hypertension; BMI: body mass index; BP: blood pressure; HTGW: hypertrigliceridemic waist; HbA1c: hemoglobina glucosilada.
Fewer patients with the HTGW phenotype adhered to the prescribed diet (69.8% vs. 81%; p < .001) and exercised regularly (44.6% vs. 58.2%; p <. 001). Conversely, more patients presented weight increases within the year prior to the study visit (29.4% vs. 22.5%; p < .001). The multiple logistic regression analysis revealed that hypertension, BMI, HbA1c, total cholesterol, LDL, and HDL cholesterol and exercise were independently associated with the HTGW phenotype (waist circumference and triglycerides, were not included in the logistic regression analysis because they are included in the definition of the HTGW phenotype).
The presence of diabetes complications according to the presence of the HTGW phenotype is shown in Fig. 1. The multivariate analysis showed that after adjusting for major cardiovascular risk factors such as age, sex, smoking, hypertension and total, LDL and HDL cholesterol, the associations between the HTGW phenotype and heart failure, peripheral arterial disease, and neuropathy remained significant (data not shown).
Regarding treatment for diabetes and its comorbidities, patients with the HTGW phenotype were more frequently prescribed antihypertensive, hypolipidemic, and antiplatelet therapies (79.7 vs. 69.1%; 87.3 vs. 62.8% and 56.2 vs. 40.4%, respectively; all p < .001). There were no differences in the percentage of patients taking insulin between both groups.
When applying the more stringent criteria for defining the HTGW phenotype (waist circumference ≥ 102 cm for men and ≥ 88 cm for women and triglyceride levels > 200 mg/dL), the percentage of patients with DM2 presenting the HTGW phenotype dropped to 14.7%. According to these criteria, patients with the HTGW phenotype presented similar differences in quantitative variables to those observed with the less stringent criteria, compared with patients without the HTGW phenotype. In terms of diabetes complications, however, the differences only remained significant for the presence of nephropathy, which was more frequent in the patients with the HTGW phenotype (data not shown).
DiscussionOur results show that 35% of patients with DM2 in Spain have the HTGW phenotype and that this patient subgroup presents poorer glycemic control, higher BMI, and a higher prevalence of diabetic complications. Despite their more frequent prescription of antihypertensive and hypolipidemic drugs, these patients show a significantly poorer lipid profile and hypertension control and a higher prevalence of diabetic complications.
The prevalence of the HTGW phenotype in the general population is approximately 19–25% and increases with age, exceeding 40% in the population over 55 years of age.19,20 Our patients with DM2 have a prevalence of the HTGW phenotype of 35% when applying the IDF criteria (waist circumference ≥ 94 cm for men and ≥ 80 cm for women and triglyceride levels > 150 mg/dL) and 14.7% when applying more stringent criteria (waist circumference ≥ 102 cm for men and ≥ 88 cm for women and triglyceride levels > 200 mg/dL). Previously reported rates in small groups with DM2 have ranged from 30% to 42%.13,14,21
These differences between studies could be due to differences in the characteristics of the study populations and in the criteria employed to define the HTGW phenotype, which reflects the lack of a universal definition. In their studies on patients with DM2, Radenkovik et al. and Sam et al.13,21 defined the HTGW phenotype as a waist circumference > 90 cm for men and > 85 cm for women and triglyceride levels > 177 mg/dL, whereas Graaf et al.14 employed a triglyceride level > 150 mg/dL and the presence of elevated waist circumference according to US criteria.
None of these studies employed the same criteria as our study, making comparisons difficult. We chose the IDF-validated criteria for elevated waist circumference for Europids,17 which we believe best fits our population, as well as the presence of triglyceride levels > 150 mg/dL, which is the cut-off established by the National Cholesterol Education Program Adult Treatment Panel II for considering the borderline-high triglyceride category.22
Our study’s main finding is that the presence of the HTGW phenotype differentiates a patient subgroup with DM2 who have poorer metabolic control and a higher risk of diabetic complications, probably due to higher visceral adiposity.12 Studies in the general population have shown that the HTGW phenotype can be as useful as the presence of metabolic syndrome for identifying individuals with deteriorated cardiometabolic risk markers.23 The definition of metabolic syndrome includes the presence of impaired glucose metabolism, and the prevalence of metabolic syndrome in patients with diabetes can therefore be as high as 90%, making it a useless classification tool for these patients.24,25 The presence of the HTGW phenotype, conversely, clearly differentiates a patient subgroup with diabetes with higher visceral adiposity and cardiometabolic risk.
Our study’s finding of an association between the HTGW phenotype and higher BMI and a poorer metabolic profile in patients with DM2 agrees with previous studies.5,13,14,21,26 According to the results of Sam et al.,13 patients with the HTGW phenotype are younger, which could reflect the fact that, for younger patients, the presence of insulin resistance becomes crucial in the development of DM2.
A few studies have demonstrated an association between the HTGW phenotype and coronary artery disease (CAD) assessed by noninvasive measures.13,14,26 St-Pierre et al.26 revealed that these patients experience their first symptoms of CAD 5 years earlier than patients without the phenotype.
We have not confirmed the association between the HTGW phenotype and a higher prevalence of clinical CAD. Our divergent findings could be due to the definition of the HTGW phenotype employed in our study, which is less stringent than that of previous studies, thereby limiting our ability to detect differences or could be due to the fact that we assessed clinically established CAD rather than subclinical CAD.
However, we found significant associations between the HTGW phenotype and other diabetes complications such as peripheral artery disease, retinopathy, nephropathy, and cardiac insufficiency. Some of these associations were independent of the presence of other cardiovascular risk factors.
An association between the HTGW phenotype and nephropathy has recently been reported in a small cross-sectional study.27 The other associations reflect novel findings in the field and could emphasize the importance of targeting multiple risk factors such as obesity and atherogenic dyslipidemia in reducing CAD and other diabetic complications.
There is evidence that patient characteristics can affect the benefits and risks of DM2 therapy.28–30 In this context, the presence or absence of the HTGW phenotype can be a useful tool for classifying DM2 into risk categories and for implementing specific therapeutic actions. Given that visceral fat can be the main causative factor for the phenotype, interventions aimed at weight loss should be a priority for this population. Several reports have demonstrated that interventions aimed at weight loss in patients with metabolic syndrome induce a greater reduction in visceral fat deposits, compared with subcutaneous fat, even with modest reductions of 5% of total weight.31 This reduction in visceral fat translates into significant metabolic improvements.32
Our finding that patients with the HTGW phenotype are less adherent to diet and exercise reflects the need to reinforce weight-loss strategies in this population. Moreover, the availability of hyperglycemic drugs that enhance weight loss, such as glucagon-like-peptide-1 receptor agonists and sodium-glucose transporter-2 inhibitors, could be especially useful for patients with HTGW when compared with patients with obesity and even metabolically healthy patients with obesity. Trials assessing the effects of these drugs in this specific population would help clarify their metabolic benefits beyond glycemic control and weight loss.
The main limitations of our study are its observational nature and lack of randomization, which precludes drawing causative conclusions. However, our sample size should be regarded as a strength, especially when compared with previous studies in populations with diabetes. Our study is one of the largest to analyze the presence of the HTGW phenotype in patients with DM2.
ConclusionsIn conclusion, the prevalence of the HTGW phenotype in the Spanish DM2 population is 35% and identifies a patient subgroup at higher cardiometabolic risk and with a higher prevalence of diabetic complications. Considering this study and others that have shown an association between HTGW phenotype and higher visceral adiposity and insulin resistance, we can speculate that the HTGW phenotype could be a simple, inexpensive and useful tool for identifying patients with DM2 who would benefit most from therapeutic strategies aimed at weight loss and cardiovascular protection.
Further prospective studies are needed to understand the predictive utility of the HTGW phenotype in the context of individualized therapy for patients with DM2.
FundingThis study was undertaken with funds provided by Almirall S.A. (Barcelona, Spain).
Conflict of interestsIM has received honoraria for speaking/consulting from Astra-Zéneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Novartis, Esteve and Sanofi-Aventis.
JSH has received honoraria for speaking/consulting from Almirall, S.A.
GC has no conflicts of interest.
ASP has no conflicts of interest.
JS is an employee of Almirall S.A.
AP has received grants from Almirall S.A. for the coordination of the study and has served as a consultant for or received lecture fees or travel reimbursement from Sanofi-Aventis, Almirall S.A., Novo Nordisk, Eli Lilly, MSD, Boehringer Ingelheim, Esteve, Bristol-Myers Squibb, Novartis, Amgen, Menarini and Astra Zeneca.
Please cite this article as: Miñambres I, Sánchez-Hernandez J, Cuixart G, Sánchez-Pinto A, Sarroca J, Pérez A. Caracterización del fenotipo de cintura hipertrigliceridémica en pacientes con diabetes mellitus tipo 2 en España: un estudio epidemiológico. Rev Clin Esp. 2021;221:576–581.