Long-term metabolic fate and mortality in obesity without metabolic syndrome

Figures & data

Table 1. The baseline characteristics of the study participants by study group.

	M-O- (n = 548)	M + O- (n = 219)	M-O+ (n = 68)	M + O+ (n = 210)	p Value	p Value <.05
Patient characteristics
Sex (female), n (%) (n = 1045)	309 (56%)	88 (40%)	33 (49%)	95 (45%)	<.001	A, C
Age (years) (n = 1045)	51 ± 6	51 ± 6	52 ± 6	52 ± 6	.187
Smoking (pack years) (n = 1045)	8 ± 12	11 ± 15	12 ± 14	13 ± 17	<.001	A, B, C
Alcohol consumption (g/week) (n = 1045)	51 ± 73	75 ± 108	60 ± 95	73 ± 105	.289
Metabolic data
Diagnosis of hypertension after baseline examinations, n (%) (n = 1045)	205 (37%)	134 (61%)	39 (57%)	162 (77%)	<.001	A, B, C, E, F
Coronary artery disease, n (%) n = 1045	31 (6%)	29 (13%)	4 (6%)	22 (10%)	<.001	A, C
Fatty liver, n (%) (n = 1028)	45 (8%)	83 (39%)	19 (28%)	134 (65%)	<.001	A, B, C, E, F
Glycaemic control (n = 1041)
Normoglycaemia, n (%)	479 (88%)	132 (61%)	59 (87%)	89 (43%)	<.001	A, C, D, E, F
Impaired fasting glucose, n (%)	2 (0%)	4 (2%)	0 (0%)	8 (4%)
Impaired glucose tolerance, n (%)	51 (9%)	48 (22%)	7 (10%)	56 (27%)
Diabetics, n (%)	14 (3%)	34 (16%)	2 (3%)	56 (27%)
MetS criteria, waist, n (%) n = 1044	147 (27%)	179 (82%)	64 (94%)	210 (100%)	<.001	A, B, C, D, E, F
MetS criteria, triglycerides, n (%), n = 1045	30 (5%)	155 (71%)	1 (1%)	138 (66%)	<.001	A, C, D, F
MetS criteria, HDL, n (%), n = 1045	52 (9%)	140 (64%)	5 (7%)	119 (57%)	<.001	A, C, D, F
MetS criteria, fasting glucose, n (%), n = 1045	31 (6%)	78 (36%)	1 (1%)	115 (55%)	<.001	A, C, D, E, F
MetS criteria, blood pressure, n (%), n = 1045	422 (77%)	212 (97%)	60 (88%)	207 (99%)	<.001	A, B, C, D, F
MetS (by IDF criteria), n (%) n = 1045	0 (0%)	179 (82%)	0 (0%)	210 (100%)	<.001	A, C, D, E, F
Waist (cm) (n = 1042)	83 ± 9	93 ± 9	101 ± 12	106 ± 10	<.001	A, B, C, D, E, F
Body mass index (kg/m^2) (n = 1045)	24.9 ± 2.4	27.0 ± 2.1	33.1 ± 3.2	34.0 ± 3.7	<.001	A, B, C, D, E
Blood pressure, systolic (mmHg) n = 1045	144 ± 22	150 ± 20	152 ± 23	158 ± 22	<.001	A, B, C, E, F
Blood pressure, diastolic (mmHg) n = 1045	86 ± 12	91 ± 11	92 ± 12	93 ± 11	<.001	A, B, C, E
Echocardiographic data
Left ventricular mass (g) (n = 945)	223 ± 77	255 ± 77	286 ± 89	300 ± 93	<.001	A, B, C, D, E
Left ventricular mass index (g/m^2) (n = 945)	125 ± 37	134 ± 39	140 ± 39	145 ± 39	<.001	A, B, C, E
Left atrial diameter (mm) (n = 896)	37 ± 5	39 ± 4	42 ± 4	43 ± 5	<.001	A, B, C, D, E
Fractional shortening (%) (n = 945)	35 ± 6	35 ± 6	35 ± 5	35 ± 6	.929
Laboratory parameters
ALT (U/L) n = 1042	25 ± 12	38 ± 27	35 ± 20	44 ± 32	<.001	A, B, C, E, F
GGT (U/L) n = 1044	31 ± 26	66 ± 116	45 ± 39	69 ± 85	<.001	A, B, C, D, E, F
Fasting glucose (mmol/L) n = 1045	4.3 ± 0.6	5.0 ± 1.7	4.3 ± 0.5	5.7 ± 2.3	<.001	A, C, D, E, F
Fasting insulin (mU/L) n = 1045	9.2 ± 5.8	15.2 ± 9.4	15.0 ± 9.2	23.2 ± 16.0	<.001	A, B, C, E, F
HOMA-IR n = 1045	1.8 ± 1.3	3.5 ± 2.9	2.9 ± 1.9	6.0 ± 5.3	<.001	A, B, C, E, F
Cholesterol (mmol/L) n = 1045	5.5 ± 1.0	6.0 ± 1.1	5.6 ± 1.1	5.8 ± 1.0	<.001	A, C, D, E
LDL-cholesterol (mmol/L) n = 1045	3.4 ± 0.9	3.8 ± 0.9	3.5 ± 1.0	3.6 ± 0.9	<.001	A, C, D, E
HDL-cholesterol (mmol/L) n = 1045	1.5 ± 0.4	1.1 ± 0.3	1.4 ± 0.3	1.1 ± 0.3	<.001	A, C, D, F
Triglycerides (mmol/L) n = 1045	1.1 ± 0.4	2.2 ± 1.2	1.2 ± 0.3	2.3 ± 1.3	<.001	A, C, D, F
Creatinine (µmol/L) n = 1043	80 ± 15	89 ± 63	80 ± 14	83 ± 14	<.001	A, C, D
GFR-Epi (mL/min) n = 1043	85 ± 15	83 ± 16	85 ± 15	84 ± 15	.804
Hs-CRP (mg/L) n = 1036	2.4 ± 4.9	4.9 ± 11.6	3.4 ± 3.4	6.4 ± 7.5	<.001	A, B, C, E, F
Adiponectin (mg/L), n = 1041	17.7 ± 7.2	13.8 ± 6.0	16.2 ± 6.5	13.2 ± 5.3	<.001	A, C, D, F
Medication
Lipid lowering drugs, n (%) n = 1045	9 (2%)	11 (5%)	1 (1%)	9 (4%)	.035	A, C
Antihypertensive medication, n (%) n = 1045	202 (37%)	139 (63%)	37 (54%)	164 (78%)	<.001	A, B, C, E, F
Acetylsalicylic acid, n (%) n = 1045	22 (4%)	19 (9%)	3 (4%)	14 (7%)	.065

The continuous variables are expressed as mean values ± standard deviation and the categorical variables as absolute numbers with percent in brackets. The differences were tested by the ANOVA test for the parametric continuous variables, Kruskall–Wallis for the non-parametric continuous variables, and Pearson chi-squared test for categorical variables. All laboratory values were taken after an overnight fast. The statistical difference for continuous variables between the groups was analysed with Tukey’s method. A p value <.05 was considered statistically significant. The pairwise comparisons with p value <.05: A, M-O- and M + O-; B, M-O- and M-O+; C, M-O- and M+O+; D, M+O- and M-O+; E, M+O- and M+O+; F, M-O + and M+O+.

The abbreviations are as follows: ALT: alanine aminotransferase; BMI: body mass index; GFR-Epi: glomerulus filtration rate by the Chronic Kidney Disease Epidemiology Collaboration equation; GGT: gamma-glutamyl transpeptidase; HDL: high-density lipoprotein; HOMA-IR: homeostatic model assessment of insulin resistance; hs-CRP: high sensitive C-reactive protein; IDF: International Diabetes Federation; LDL: low-density lipoprotein; MetS: metabolic syndrome; M-O-: no metabolic syndrome or obesity; M + O-: metabolic syndrome without obesity; M-O+: obesity without metabolic syndrome; M+O+: metabolic syndrome and obesity

Figure 1. The cumulative survival of total mortality (A), cardiovascular (B) and atrial fibrillation (C) in the study groups. The curve separations were tested by log rank test and were statistically significant in 1 A between M-O- and M+O-***, M-O- and M+O+*** in 1B between M-O- and M+O-***, M-O- and M+O+***, M-O + and M+O-**, M-O + and M+O+* in 1 C between M-O- and M+O+***, M+O- and M+O+**, M-O + and M+O+*. M: metabolic syndrome; O: obesity; -: condition does not exist; +: condition exists. *log-rank < 0.05, **log-rank < 0.01, ***log-rank < 0.001.

Table 2. Mortality, cardiovascular events and atrial fibrillation in the study groups.

	M-O- (n = 548)	M+O- (n = 219)	M-O+ (n = 68)	M+O+ (n = 210)
Total mortality rate	162 (30%)	96 (44%)	26 (38%)	102 (49%)
Hazard ratio	–	1.729 (1.343–2.226)***	1.390 (0.918–2.103)	1.961 (1.530–2.514)***
Multivariable hazard ratio, model 1	–	1.368 (1.052–1.779)*	1.010 (0.661–1.543)	1.577 (1.219–2.038)**
Multivariable hazard ratio, model 2	–	1.414 (1.055–1.897)*	1.079 (0.684–1.701)	1.450 (1.056–1.991)*
Cardiovascular events	92 (17%)	80 (37%)	12 (18%)	71 (34%)
Hazard ratio	–	2.637 (1.954–3.559)***	1.087 (0.596–1.985)	2.341 (1.717–3.192)***
Multivariable hazard ratio, model 1	–	2.089 (1.535–2.841)***	0.833 (0.453–1.529)	1.951 (1.419–2.683)***
Multivariable hazard ratio, model 2	–	2.127 (1.517–2.981)***	0.630 (0.315–1.262)	1.533 (1.049–2.240)*
Atrial fibrillation incidence	58 (11%)	26 (12%)	7 (10%)	49 (23%)
Hazard ratio	–	1.226 (0.772–1.947)	0.984 (0.449–2.156)	2.557 (1.747–3.743)***
Multivariable hazard ratio, model 1	–	1.120 (0.692–1.812)	0.779 (0.353–1.717)	2.235 (1.516–3.295)***
Multivariable hazard ratio, model 2	–	0.977 (0.562–1.699)	0.582 (0.253–1.339)	1.625 (0.959–2.752)

All hazard ratios are calculated with M-O- as the reference group. Multivariable hazard ratio model 1 is adjusted for age, sex, smoking (pack years), amount of alcohol consumption and LDL cholesterol. Multivariable hazard ratio 2 is adjusted for multivariable hazard ratio model 1 + hs-CRP, adiponectin and left ventricular mass index (total mortality and cardiovascular events)/left atrial diameter (atrial fibrillation).

M-O-: no metabolic syndrome or obesity; M+O-: metabolic syndrome without obesity; M-O+: obesity without metabolic syndrome; M+O+: metabolic syndrome and obesity.

*p < .05, **p < 0.01, ***p < .001.

Figure 2. The Sankey diagram of death rates and metabolic sustainability and transition between the groups. The subjects who were still alive at the time of the control visit (31 December 2014) but had not attended the control visit were excluded from the graph. MetS, metabolic syndrome.

Data availability statement

The data used in this study are not publicly available due to health data confidentiality concerns. Possible requests or questions can be sent to prof. Olavi Ukkola.