The objective of this study to develop percentile curves for cardiometabolic disease markers in a population-based sample of Canadian children and youth.
Methods
The analysis used data from 6116 children and adolescents between 6 and 19 years of age who participated in the Canadian Health Measures Survey cycles 1 (2007/2009), 2 (2009/2011), and 3 (2012/2013). Total cholesterol, HDL cholesterol, and hemoglobin A1c levels as well as fasting levels of triglycerides, insulin, and homeostasis model assessment insulin resistance were measured using standardized procedures. Age- and sex-specific centiles for all markers were calculated using Cole and Green’s LMS method.
Results
With the exception of hemoglobin A1c, all markers showed age- and sex-related differences during childhood and adolescence.
Conclusions
We have developed centile curves for cardiometabolic disease markers in Canadian children and adolescents and demonstrated age and sex differences that should be considered when evaluating these markers in this age group.
Abkürzungen
CHMS
Canadian Health Measures Survey
CVD
Cardiovascular disease
HbA1c
Hemoglobin A1c
HDL
High-density lipoprotein
HOMA-IR
Homeostasis model assessment insulin resistance
LMS
Lambda Mu Sigma
Background
Cardiovascular disease (CVD) is currently the leading cause of death worldwide [1]. With the exception of congenital heart disease, CVD manifests in adulthood, but its risk factors are already detectable in childhood. Abnormal blood lipids and diabetes are among the risk factors for the development of CVD [2, 3]. An abnormal lipid profile can include elevated total cholesterol, elevated triglycerides, and low high-density lipoprotein (HDL) cholesterol. Insulin resistance plays an important role in the development of youth-onset type 2 diabetes, an emerging disease in children and youth [4]. Homeostasis model assessment estimates insulin resistance (HOMA-IR) from fasting levels of insulin and glucose [5]; other measures that have been used to identify insulin resistance or diabetes include fasting insulin and glycosylated hemoglobin (HbA1c), respectively [6‐8].
Levels of these markers vary by sex and across age in childhood and adolescence, and percentile curves have been developed to describe their physiologic development. Percentile curves have been published for lipids and markers of insulin resistance in various populations [9‐14]. Since these curves are specific to populations and there are no percentile curves for the levels of these markers in Canadian children, the objective of this study was to develop percentile curves for cardiometabolic markers in a population-based sample of Canadian children and youth.
Anzeige
Methods
Study design
This study used data of children and youth aged 6 to 19 years from the Canadian Health Measures Survey (CHMS) cycles 1 to 3, a representative, cross-sectional survey assessing health and wellness in Canadians [15‐17]. The survey includes a household interview to obtain sociodemographic and health information and a visit to a mobile examination centre to perform physical measurements and tests. The sampling frame of the Canadian Labour Force Survey was used to identify the collection sites for the mobile examination centres. Within each collection site, households were selected using the 2006 Census as the sampling frame. Interviews and examinations for the CHMS Cycle 1 were performed between 2007 and 2009, for Cycle 2 between 2009 and 2011, and for Cycle 3 between 2012 and 2013. Household response rates were 69.6, 75.9, and 74.1%, respectively; final response rates in the 3 cycles were 51.7, 55.7 and 51.7%, respectively [15‐17]. We combined data from the 3 cycles as per Statistics Canada guidelines [18]. A total of 11,999 persons participated in physical examination part of the three survey cycles. The present analysis uses data from 6116 children and adolescents between 6 and 19 years of age.
The Health Canada Research Ethics Board gave approval for the CHMS. All participants gave written informed consent; parents or guardians consented on behalf of children aged 6 to 13 years, and the child provided their assent to participate; youth 14 to 17 years consented on their own, but their parents or guardians had to give verbal permission for the household interview [15]. The current project was approved by the IWK Health Centre Research Ethics Board, Halifax, NS, Canada (File # 1014413).
Laboratory measurements
Blood for measurement of cardiometabolic markers was collected by standard venipuncture. Fasted blood samples for measurement of insulin, glucose, and triglycerides were taken in a randomly selected sample of participants. The sample was obtained by randomly offering each respondent a clinic appointment either in the morning (after an overnight fast) or in the afternoon (non-fasted) [15]. Blood samples were centrifuged within 2 h and aliquoted within 4 h of collection. The samples were stored either in the refrigerator or in the freezer until shipping. Samples were shipped once a week to the Health Canada reference laboratory in Ottawa. Participants with diabetes were excluded from the analysis of insulin, HOMA-IR, and HbA1c; participants taking lipid-lowering medication were excluded from the analysis of lipids. Levels of total cholesterol, HDL cholesterol, triglycerides, and glucose were measured using a colorimetric test and HbA1c was measured using a immunoturbidimetric test on the Vitros 5,1FS (Ortho Clinical Diagnostics, Markham, ON, Canada). Fasting insulin levels were determined using a solid-phase, two-site chemiluminescent immunometric assay on the Advia Centaur XP (Siemens, Erlangen, Germany). Since insulin measurements in cycle 1 were performed using a different method and had a considerable proportion of levels below the test’s limit of detection, we only used insulin measurements from cycles 2 and 3 in the present analysis. Fasting insulin and glucose levels were used to calculate HOMA-IR as (fasting insulin [μU/L] x glucose [mmol/L]) / 22.5 [19].
Statistical analysis
Percentile curves for total cholesterol, HDL cholesterol, triglycerides, insulin, HOMA-IR, and HbA1c were modeled using the LMS method by Cole and Green [20]. We have described the LMS method in detail elsewhere [21]. Briefly, the method uses a Box-Cox transformation to normalize the data and models the mean (M), variance (S), and skewness (L) as parameters over age using cubic splines. Centiles and z-scores for the truncated standard normal distribution can then be determined from the three parameters at each age [20]. We calculated the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th centile for each marker. Models were fit to data from respondents up to age 30 years to avoid unusual behaviour of the spline functions near the end of the age range. The goodness of fit for each model was assessed using residual quantile plots (“worm plots”) [22]. All calculations were performed using sample weights provided by Statistics Canada to account for the design effect and reduce non-response bias. The statistical software package R [23] with the gamlss package [24] was used to perform the statistical analyses.
Anzeige
Results
Sociodemographic characteristics of the sample are summarized in Table 1. Figures 1, 2, 3, 4, 5 and 6 and Tables 2, 3, 4, 5, 6 and 7 show the percentile curves and their values for total cholesterol, HDL cholesterol, triglycerides, insulin, HOMA-IR, and HbA1c.
Table 1
Characteristics of 6116 Canadian children and youth aged 6 to 19 years in the Canadian Health Measures Survey Cycles 1 to 3
Prevalence [%]
Sex
Male
51.6
Female
48.4
Region of Canada
Atlantic Canada
6.7
Québec
22.5
Ontario
40.5
Prairies
18.2
British Columbia
12.2
Racial origin
White
80.9
Black
5.9a
Asian
10.7a
Other
2.4a
Weight status (IOTF)
Underweight
7.5
Normal weight
65.6
Overweight
17.4
Obese
9.5
Household education
Secondary school or less
15.7
College
46.6
University
37.6
Household income
$30,000 or less
15.1
$30,001 - $60,000
22.8
$60,001 - $80,000
18.3
$80,001 - $100,000
16.3
> $100,000
27.5
Abbreviations: IOTF International Obesity Task Force
aCoefficient of variation between 16.6 and 33.3%; interpret with caution as per Statistics Canada sampling variability reporting guidelines
Fig. 1
Percentile curves for total cholesterol levels for male and female Canadian children and youth aged 6 to 19 years
Fig. 2
Percentile curves for high-density lipoprotein (HDL) cholesterol levels for male and female Canadian children and youth aged 6 to 19 years
Fig. 3
Percentile curves for triglyceride levels for male and female Canadian children and youth aged 6 to 19 years
Fig. 4
Percentile curves for insulin levels for male and female Canadian children and youth aged 6 to 19 years
Fig. 5
Percentile curves for homeostasis model assessment insulin resistance (HOMA-IR) levels for male and female Canadian children and youth aged 6 to 19 years
Fig. 6
Percentile curves for hemoglobin A1c levels for male and female Canadian children and youth aged 6 to 19 years
Table 2
L, M, and S values, and percentiles of total cholesterol [mmol/L] by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
203
1.2662
4.0824
0.1676
2.73
3.18
3.61
4.08
4.54
4.94
5.32
7
184
1.0339
4.1657
0.1666
2.85
3.27
3.70
4.17
4.63
5.05
5.46
8
215
0.7986
4.2255
0.1654
2.96
3.35
3.76
4.23
4.70
5.14
5.58
9
233
0.5790
4.2369
0.1645
3.01
3.38
3.78
4.24
4.72
5.17
5.63
10
256
0.3985
4.2026
0.1642
3.02
3.37
3.75
4.20
4.68
5.14
5.62
11
283
0.2725
4.1427
0.1646
3.00
3.33
3.70
4.14
4.62
5.09
5.58
12
187
0.2000
4.0742
0.1658
2.95
3.28
3.64
4.07
4.55
5.02
5.51
13
178
0.1564
4.0321
0.1673
2.92
3.24
3.60
4.03
4.51
4.98
5.48
14
170
0.1308
4.0222
0.1691
2.91
3.23
3.59
4.02
4.50
4.98
5.49
15
175
0.1173
4.0342
0.1717
2.90
3.23
3.59
4.03
4.53
5.01
5.54
16
178
0.1121
4.0701
0.1746
2.91
3.24
3.61
4.07
4.58
5.08
5.62
17
186
0.1066
4.1326
0.1769
2.94
3.28
3.66
4.13
4.65
5.17
5.73
18
168
0.1017
4.2050
0.1788
2.99
3.33
3.72
4.21
4.74
5.27
5.85
19
152
0.0901
4.2612
0.1809
3.02
3.37
3.77
4.26
4.81
5.36
5.96
Male
6
203
1.1968
4.0369
0.1508
2.86
3.24
3.62
4.04
4.44
4.80
5.15
7
211
0.8365
4.0884
0.1523
2.95
3.30
3.67
4.09
4.51
4.90
5.29
8
232
0.5410
4.1350
0.1551
3.01
3.35
3.71
4.13
4.58
4.99
5.42
9
239
0.3792
4.1691
0.1597
3.03
3.37
3.73
4.17
4.63
5.08
5.54
10
263
0.3624
4.1766
0.1651
3.00
3.35
3.73
4.18
4.66
5.12
5.61
11
277
0.3556
4.1469
0.1703
2.95
3.30
3.69
4.15
4.64
5.12
5.62
12
207
0.3332
4.0711
0.1757
2.87
3.22
3.61
4.07
4.57
5.06
5.57
13
207
0.3217
3.9598
0.1801
2.77
3.12
3.50
3.96
4.46
4.95
5.46
14
205
0.2648
3.8546
0.1833
2.69
3.02
3.40
3.85
4.35
4.84
5.36
15
184
0.1878
3.7910
0.1863
2.64
2.97
3.34
3.79
4.29
4.79
5.32
16
208
0.1426
3.7735
0.1886
2.62
2.95
3.32
3.77
4.28
4.79
5.33
17
183
0.1015
3.7992
0.1883
2.65
2.98
3.34
3.80
4.31
4.82
5.38
18
144
0.0557
3.8565
0.1873
2.70
3.03
3.40
3.86
4.37
4.90
5.47
19
139
0.0083
3.9299
0.1869
2.76
3.09
3.46
3.93
4.46
4.99
5.58
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
Table 3
L, M, and S values, and percentiles of HDL cholesterol [mmol/L] by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
203
0.6653
1.2995
0.2301
0.78
0.94
1.10
1.30
1.51
1.70
1.90
7
184
0.5810
1.3513
0.2315
0.82
0.98
1.15
1.35
1.57
1.78
1.99
8
215
0.4894
1.3925
0.2317
0.85
1.01
1.18
1.39
1.62
1.84
2.07
9
233
0.4025
1.4128
0.2304
0.88
1.03
1.20
1.41
1.64
1.87
2.11
10
256
0.3317
1.4069
0.2269
0.89
1.04
1.20
1.41
1.63
1.86
2.10
11
283
0.2946
1.3835
0.2222
0.89
1.03
1.19
1.38
1.60
1.82
2.05
12
187
0.2932
1.3527
0.2180
0.87
1.01
1.16
1.35
1.56
1.77
1.99
13
178
0.2666
1.3372
0.2152
0.87
1.00
1.15
1.34
1.54
1.74
1.96
14
170
0.1991
1.3404
0.2145
0.88
1.01
1.16
1.34
1.55
1.75
1.98
15
175
0.1202
1.3502
0.2156
0.89
1.02
1.17
1.35
1.56
1.77
2.01
16
178
0.0477
1.3590
0.2180
0.90
1.03
1.17
1.36
1.57
1.79
2.04
17
186
−0.0261
1.3764
0.2213
0.91
1.04
1.19
1.38
1.60
1.83
2.09
18
168
−0.0758
1.4019
0.2258
0.92
1.05
1.20
1.40
1.63
1.88
2.16
19
152
−0.0551
1.4209
0.2316
0.92
1.06
1.22
1.42
1.66
1.92
2.21
Male
6
203
0.8228
1.4346
0.2226
0.86
1.04
1.22
1.43
1.65
1.85
2.06
7
211
0.6385
1.4440
0.2207
0.89
1.06
1.23
1.44
1.66
1.87
2.09
8
232
0.4626
1.4509
0.2215
0.91
1.07
1.24
1.45
1.68
1.89
2.12
9
239
0.3069
1.4533
0.2256
0.92
1.07
1.24
1.45
1.69
1.92
2.17
10
263
0.1937
1.4465
0.2296
0.92
1.07
1.24
1.45
1.68
1.93
2.19
11
277
0.1465
1.4230
0.2297
0.91
1.05
1.22
1.42
1.66
1.90
2.16
12
207
0.1687
1.3827
0.2281
0.89
1.02
1.18
1.38
1.61
1.84
2.09
13
207
0.2352
1.3335
0.2266
0.85
0.99
1.14
1.33
1.55
1.77
2.00
14
205
0.3157
1.2882
0.2251
0.82
0.95
1.10
1.29
1.49
1.70
1.92
15
184
0.3915
1.2523
0.2244
0.79
0.92
1.07
1.25
1.45
1.64
1.85
16
208
0.4549
1.2270
0.2256
0.77
0.90
1.05
1.23
1.42
1.61
1.81
17
183
0.4843
1.2122
0.2260
0.75
0.89
1.03
1.21
1.40
1.59
1.78
18
144
0.4698
1.2062
0.2245
0.75
0.89
1.03
1.21
1.40
1.58
1.77
19
139
0.4299
1.2084
0.2234
0.76
0.89
1.03
1.21
1.40
1.58
1.78
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
Table 4
L, M, and S values, and percentiles of triglycerides [mmol/L] by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
78
−0.0198
0.7390
0.3934
0.35
0.45
0.57
0.74
0.96
1.23
1.56
7
85
− 0.0360
0.7567
0.3932
0.36
0.46
0.58
0.76
0.99
1.26
1.60
8
98
−0.0522
0.7744
0.3931
0.37
0.47
0.60
0.77
1.01
1.29
1.65
9
127
−0.0680
0.7922
0.3931
0.39
0.48
0.61
0.79
1.04
1.32
1.69
10
114
−0.0821
0.8100
0.3931
0.40
0.49
0.62
0.81
1.06
1.35
1.74
11
139
−0.0928
0.8273
0.3932
0.40
0.51
0.64
0.83
1.08
1.39
1.78
12
93
−0.0987
0.8438
0.3935
0.41
0.52
0.65
0.84
1.10
1.42
1.82
13
88
− 0.0996
0.8593
0.3942
0.42
0.52
0.66
0.86
1.13
1.44
1.86
14
88
−0.0958
0.8738
0.3954
0.43
0.53
0.67
0.87
1.14
1.47
1.89
15
91
−0.0874
0.8874
0.3972
0.43
0.54
0.68
0.89
1.16
1.49
1.92
16
91
−0.0746
0.9003
0.3996
0.43
0.54
0.69
0.90
1.18
1.52
1.95
17
89
−0.0581
0.9125
0.4026
0.43
0.55
0.70
0.91
1.20
1.54
1.98
18
74
−0.0389
0.9240
0.4061
0.44
0.55
0.70
0.92
1.22
1.56
2.01
19
72
−0.0180
0.9346
0.4102
0.43
0.55
0.71
0.93
1.23
1.58
2.03
Male
6
102
−0.2816
0.6737
0.4053
0.34
0.41
0.52
0.67
0.90
1.18
1.59
7
98
−0.2348
0.6849
0.4111
0.34
0.42
0.52
0.68
0.91
1.20
1.61
8
116
−0.1881
0.6961
0.4169
0.33
0.42
0.53
0.70
0.93
1.22
1.63
9
120
−0.1418
0.7075
0.4227
0.33
0.42
0.54
0.71
0.95
1.24
1.64
10
133
−0.0967
0.7195
0.4281
0.33
0.42
0.54
0.72
0.96
1.26
1.66
11
135
−0.0544
0.7322
0.4329
0.33
0.42
0.55
0.73
0.98
1.29
1.68
12
96
−0.0165
0.7459
0.4368
0.33
0.43
0.56
0.75
1.00
1.31
1.71
13
112
0.0157
0.7606
0.4395
0.33
0.43
0.57
0.76
1.02
1.33
1.73
14
97
0.0421
0.7763
0.4412
0.33
0.44
0.58
0.78
1.04
1.36
1.75
15
93
0.0630
0.7927
0.4422
0.34
0.45
0.59
0.79
1.07
1.38
1.78
16
103
0.0788
0.8098
0.4428
0.34
0.45
0.60
0.81
1.09
1.41
1.81
17
92
0.0899
0.8275
0.4431
0.35
0.46
0.61
0.83
1.11
1.44
1.85
18
78
0.0968
0.8457
0.4435
0.35
0.47
0.62
0.85
1.14
1.47
1.89
19
74
0.0999
0.8642
0.4441
0.36
0.48
0.64
0.86
1.16
1.50
1.93
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
Table 5
L, M, and S values, and percentiles of insulin [pmol/L] by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
74
0.0810
36.8032
0.5822
11.69
17.05
24.69
36.80
54.17
75.94
105.08
7
85
0.0832
41.9738
0.5661
13.77
19.86
28.47
41.97
61.13
84.90
116.43
8
95
0.0861
47.1805
0.5505
15.95
22.79
32.35
47.18
68.00
93.58
127.19
9
124
0.0909
52.4480
0.5352
18.25
25.83
36.33
52.45
74.82
102.02
137.42
10
110
0.0997
57.6269
0.5201
20.59
28.91
40.32
57.63
81.35
109.87
146.55
11
136
0.1121
62.4301
0.5044
22.90
31.91
44.13
62.43
87.17
116.52
153.78
12
92
0.1263
66.5218
0.4884
25.06
34.66
47.52
66.52
91.86
121.50
158.64
13
88
0.1414
69.6293
0.4734
26.89
36.93
50.22
69.63
95.15
124.61
161.05
14
86
0.1553
71.6632
0.4607
28.26
38.58
52.12
71.66
97.07
126.08
161.58
15
86
0.1652
72.6769
0.4515
29.11
39.56
53.17
72.68
97.82
126.30
160.90
16
90
0.1703
72.8110
0.4465
29.42
39.88
53.45
72.81
97.67
125.70
159.62
17
86
0.1707
72.2282
0.4460
29.21
39.58
53.04
72.23
96.85
124.61
158.18
18
74
0.1665
71.1378
0.4500
28.57
38.80
52.10
71.14
95.65
123.38
157.03
19
71
0.1592
69.7465
0.4583
27.60
37.65
50.80
69.75
94.31
122.28
156.42
Male
6
98
−0.0050
29.2964
0.5269
10.90
14.93
20.54
29.30
41.81
57.62
79.12
7
95
−0.0012
33.2034
0.5309
12.24
16.82
23.21
33.20
47.50
65.58
90.17
8
116
0.0028
37.0587
0.5348
13.54
18.66
25.83
37.06
53.14
73.49
101.18
9
118
0.0065
40.8164
0.5385
14.78
20.44
28.37
40.82
58.67
81.26
112.00
10
130
0.0097
44.7223
0.5419
16.06
22.28
31.01
44.72
64.42
89.36
123.31
11
129
0.0126
49.2160
0.5451
17.54
24.40
34.05
49.22
71.02
98.66
136.29
12
95
0.0153
54.1827
0.5477
19.18
26.75
37.41
54.18
78.32
108.91
150.58
13
110
0.0178
58.6671
0.5499
20.65
28.87
40.44
58.67
84.91
118.19
163.49
14
95
0.0203
61.7110
0.5519
21.61
30.27
42.47
61.71
89.42
124.55
172.38
15
91
0.0232
62.9131
0.5539
21.91
30.75
43.23
62.91
91.27
127.21
176.13
16
102
0.0271
62.5506
0.5561
21.65
30.46
42.90
62.55
90.85
126.71
175.45
17
91
0.0318
61.1922
0.5583
21.03
29.67
41.90
61.19
88.97
124.15
171.90
18
76
0.0370
59.3041
0.5602
20.25
28.65
40.54
59.30
86.30
120.44
166.70
19
74
0.0431
57.1325
0.5615
19.39
27.51
39.00
57.13
83.18
116.05
160.46
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
Table 6
L, M, and S values, and percentiles of HOMA-IR by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
74
0.0680
1.0304
0.6120
0.31
0.46
0.68
1.03
1.55
2.21
3.12
7
85
0.0816
1.1930
0.5955
0.37
0.54
0.79
1.19
1.77
2.50
3.48
8
95
0.0953
1.3607
0.5795
0.43
0.63
0.91
1.36
2.00
2.79
3.84
9
124
0.1090
1.5413
0.5642
0.50
0.73
1.04
1.54
2.24
3.09
4.21
10
110
0.1226
1.7284
0.5496
0.57
0.83
1.18
1.73
2.48
3.40
4.57
11
136
0.1354
1.9044
0.5360
0.64
0.93
1.31
1.90
2.71
3.67
4.90
12
92
0.1467
2.0481
0.5235
0.71
1.01
1.43
2.05
2.89
3.88
5.14
13
88
0.1557
2.1435
0.5125
0.75
1.07
1.50
2.14
3.00
4.01
5.26
14
86
0.1619
2.1886
0.5036
0.78
1.11
1.54
2.19
3.05
4.04
5.28
15
86
0.1645
2.1908
0.4970
0.79
1.12
1.55
2.19
3.04
4.02
5.23
16
90
0.1635
2.1612
0.4930
0.79
1.11
1.54
2.16
2.99
3.94
5.12
17
86
0.1591
2.1092
0.4916
0.78
1.09
1.50
2.11
2.91
3.84
5.00
18
74
0.1514
2.0465
0.4928
0.75
1.05
1.46
2.05
2.83
3.74
4.87
19
71
0.1411
1.9837
0.4965
0.73
1.02
1.41
1.98
2.75
3.65
4.77
Male
6
98
0.0558
0.8427
0.5725
0.28
0.40
0.57
0.84
1.23
1.73
2.40
7
95
0.0576
0.9718
0.5752
0.32
0.46
0.66
0.97
1.43
2.00
2.78
8
116
0.0595
1.1004
0.5778
0.36
0.52
0.74
1.10
1.62
2.27
3.15
9
118
0.0610
1.2255
0.5802
0.40
0.57
0.82
1.23
1.80
2.54
3.52
10
130
0.0617
1.3545
0.5823
0.44
0.63
0.91
1.35
2.00
2.81
3.91
11
129
0.0619
1.5014
0.5841
0.48
0.70
1.01
1.50
2.22
3.12
4.35
12
95
0.0618
1.6614
0.5855
0.53
0.77
1.11
1.66
2.45
3.46
4.82
13
110
0.0618
1.8031
0.5864
0.58
0.84
1.21
1.80
2.67
3.76
5.24
14
95
0.0619
1.8974
0.5873
0.60
0.88
1.27
1.90
2.81
3.96
5.52
15
91
0.0627
1.9332
0.5883
0.61
0.89
1.29
1.93
2.86
4.04
5.63
16
102
0.0646
1.9204
0.5896
0.61
0.89
1.28
1.92
2.84
4.02
5.60
17
91
0.0673
1.8754
0.5910
0.59
0.86
1.25
1.88
2.78
3.93
5.48
18
76
0.0705
1.8126
0.5922
0.57
0.83
1.21
1.81
2.69
3.80
5.30
19
74
0.0747
1.7406
0.5929
0.54
0.80
1.16
1.74
2.58
3.64
5.08
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
Table 7
L, M, and S values, and percentiles of hemoglobin A1c by age and sex for Canadian children and youth aged 6 to 19 years
Sex
Age
n
L
M
S
3rd
10th
25th
50th
75th
90th
97th
Female
6
192
0.6293
0.0531
0.0565
0.0476
0.0493
0.0511
0.0531
0.0552
0.0570
0.0589
7
178
0.0341
0.0532
0.0563
0.0478
0.0495
0.0512
0.0532
0.0552
0.0571
0.0591
8
204
−0.5398
0.0532
0.0561
0.0480
0.0496
0.0513
0.0532
0.0553
0.0573
0.0593
9
224
−1.0745
0.0533
0.0560
0.0482
0.0497
0.0513
0.0533
0.0553
0.0574
0.0596
10
248
−1.5959
0.0533
0.0560
0.0484
0.0498
0.0514
0.0533
0.0554
0.0575
0.0598
11
275
−2.1144
0.0533
0.0559
0.0485
0.0499
0.0514
0.0533
0.0554
0.0576
0.0600
12
184
−2.5527
0.0533
0.0558
0.0486
0.0499
0.0514
0.0533
0.0554
0.0577
0.0602
13
172
−2.8025
0.0532
0.0557
0.0486
0.0499
0.0514
0.0532
0.0554
0.0576
0.0603
14
166
−2.8388
0.0531
0.0555
0.0485
0.0498
0.0513
0.0531
0.0553
0.0575
0.0601
15
167
−2.7545
0.0530
0.0553
0.0484
0.0497
0.0512
0.0530
0.0551
0.0574
0.0599
16
172
−2.6052
0.0529
0.0551
0.0483
0.0496
0.0511
0.0529
0.0550
0.0572
0.0597
17
177
−2.4044
0.0528
0.0550
0.0481
0.0495
0.0509
0.0528
0.0549
0.0570
0.0595
18
165
−2.1906
0.0527
0.0550
0.0480
0.0494
0.0509
0.0527
0.0548
0.0569
0.0593
19
149
−2.0342
0.0527
0.0552
0.0479
0.0493
0.0508
0.0527
0.0548
0.0569
0.0592
Male
6
195
−0.4642
0.0530
0.0619
0.0473
0.0490
0.0509
0.0530
0.0553
0.0575
0.0598
7
205
−0.5917
0.0532
0.0612
0.0476
0.0492
0.0510
0.0532
0.0554
0.0576
0.0599
8
227
−0.7384
0.0533
0.0605
0.0478
0.0494
0.0512
0.0533
0.0555
0.0577
0.0600
9
229
−0.8769
0.0534
0.0598
0.0480
0.0496
0.0513
0.0534
0.0556
0.0578
0.0601
10
256
−0.9903
0.0535
0.0591
0.0481
0.0497
0.0514
0.0535
0.0557
0.0578
0.0601
11
267
−1.0740
0.0535
0.0584
0.0482
0.0498
0.0515
0.0535
0.0557
0.0579
0.0602
12
204
−1.1009
0.0535
0.0580
0.0483
0.0498
0.0515
0.0535
0.0557
0.0578
0.0601
13
201
−1.0887
0.0535
0.0577
0.0483
0.0498
0.0515
0.0535
0.0556
0.0578
0.0600
14
203
−1.0467
0.0534
0.0574
0.0482
0.0497
0.0514
0.0534
0.0555
0.0576
0.0599
15
180
−1.0081
0.0532
0.0571
0.0481
0.0496
0.0512
0.0532
0.0554
0.0574
0.0596
16
205
−0.9894
0.0530
0.0567
0.0479
0.0494
0.0511
0.0530
0.0551
0.0572
0.0594
17
180
−1.0085
0.0528
0.0561
0.0478
0.0493
0.0509
0.0528
0.0549
0.0569
0.0591
18
138
−1.0586
0.0527
0.0555
0.0477
0.0492
0.0508
0.0527
0.0547
0.0567
0.0588
19
135
−1.1174
0.0526
0.0549
0.0477
0.0491
0.0507
0.0526
0.0546
0.0566
0.0587
Abbreviations: L lambda (skewness); M mu (mean); S sigma (variance)
×
×
×
×
×
×
Total cholesterol curves had a bimodal distribution for both boys and girls. Overall, cholesterol levels were slightly higher in girls than in boys. Median levels at 6 years were 4.1 mmol/L in girls and 4.0 mmol/L in boys. In boys, the 50th centile peaked at age 10 years (4.2 mmol/L). The lowest median cholesterol level in boys was seen at 16 years of age (3.8 mmol/L), after which it increased to 3.9 mmol/L at 19 years. In girls, the 50th centile for cholesterol had a peak at 9 years (4.2 mmol/L), decreased to a trough at 15 years (4.0 mmol/L) and increased again to 4.3 mmol/L at 19 years of age. HDL cholesterol showed a bimodal distribution in girls, but only one peak in boys. In boys, the median levels were highest before 11 years (1.5 mmol/L) and then steadily declined until 19 years (1.2 mmol/L). Median HDL cholesterol in girls peaked at age 10 years (1.4 mmol/L) and after a trough (1.3 mmol/L) increased again to 1.4 mmol/L at 19 years. Median levels of triglycerides exhibited a steady linear increase from 6 years (0.7 mmol/L) to 19 years (0.9 mmol/L) for both sexes. Insulin levels were overall higher in girls than in boys. For both sexes, median levels increased until about 14 years of age (62 and 72 pmol/L in boys and girls, respectively), after which they slightly decreased to 57 pmol/L in boys and 70 pmol/L in girls at 19 years of age. Centile curves for HOMA-IR largely mirrored those for insulin with the 50th percentile peaking at 15 years for both sexes (1.9 for boys and 2.2 for girls). Median HbA1c levels held nearly constant around 5.3% from 6 to 19 years for both sexes.
Discussion
The objective of this study was to develop percentile curves for total cholesterol, HDL cholesterol, triglycerides, insulin, HOMA-IR, and HbA1c in a population-based sample of Canadian children and youth. We found age- and sex-related differences in blood levels for all markers except for HbA1c.
A bimodal shape of the centile curves for total cholesterol levels has been described in various Western populations [9, 11, 13, 25]. A pre-adolescent peak at around 8 to 10 years of age that is more pronounced in boys is followed by a decrease during adolescence and another peak in late adolescence and young adulthood. The same pattern, but without a post-pubertal rise in boys, can be seen for HDL cholesterol [9, 11, 13]. The pubertal trough of cholesterol levels may be the result of the well described insulin resistance during puberty [26]. Clinicians should be aware of these physiologic changes when interpreting cholesterol levels. However, it should also be acknowledged that median levels of cholesterol in our study as well as in other studies varied by 10% or less in either direction during childhood and adolescence [9, 11, 13, 25].
Median triglyceride levels in our sample showed a nearly linear increase by about 30% from around 0.7 to 0.9 mmol/L in both sexes during childhood and adolescence. Some investigators previously described a bimodal pattern in girls with peaks at around 12 and 19 years of age [9, 11], while others also reported the linear increase we found [13]. These differences may be explained by different degrees of smoothing applied during the modeling process.
Median fasting insulin levels were higher in girls than in boys, and levels in both sexes peaked at around 15 years of age followed by a slight decrease towards late adolescence. Similar age and sex differences have also been reported by others [13, 27]. The peak in puberty reflects the physiologically reduced insulin sensitivity and concomitant increase in insulin secretion during that period [28, 29]. The median insulin levels in our study and others [12, 13, 27] varied with pubertal levels ranging from 52 to 63 pmol/L in boys and from 65 to 73 pmol/L in girls. These differences may be explained by differences in the insulin assay used [30] or differences in the body composition, ethnicity, and puberty stage of the children in the sample. The shape of the HOMA-IR curves was similar to those for fasting insulin. Schwartz et al. found a significant correlation between fasting insulin and HOMA-IR but found both only modestly correlated with the insulin resistance measurement gold standard, the euglycemic-hyperinsulinemic glucose clamp [31]. HOMA-IR still is among the most commonly used surrogate measure of insulin resistance to date. Given the variation over sex and age, in particular the physiologic insulin resistance in puberty, the use of an age- and sex-specific percentile-based cutoff for HOMA-IR is warranted. Unfortunately, such a cutoff has not been established to date [32].
Glycosylated hemoglobin or HbA1c is an established marker for long-term glycemic control in patients with diabetes [33]. HbA1c has been proposed as a screening tool for undiagnosed diabetes in adults [6] and children with overweight or obesity [8], but the evidence is still very limited. We found very little change in HbA1c levels from childhood to late adolescence, and there was no difference between the sexes. To the best of our knowledge, only three previous studies have examined HbA1c levels during childhood [12, 14, 34]. Only Peplies et al. in the European IDEFICS cohort developed percentile curves to describe the changes in levels across age and found a 15% increase in median HbA1c levels between 7 and 11 years for both sexes [12].
The strengths of our study include the use of a large population-based sample and the use of standardized protocols and procedures for the measurement of the cardiometabolic marker levels. A shortcoming of the use of cross-sectional data is that it is not clear if the trajectories of individual children follow this pattern; longitudinal data may be more accurate in describing age-related changes but are considerably more resource intensive to collect at the population level. Due to the relatively small proportion of visible minority children in the sample (< 20%), we were not able to investigate ethnic differences in marker levels and trajectories. Another limitation of our study is that we were unable to take puberty stage, which may influence insulin and lipid levels, into account as this information was not available in the CHMS. By contrast to some of the previous studies in this area, we did not restrict our analysis to children with a healthy weight [9, 12], as our goal was to describe population-based trajectories. Since the inclusion of overweight and obese children in our sample may have influenced lipid and insulin levels, our percentiles cannot be considered as reference values.
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Conclusions
Our study has developed percentile curves for cardiometabolic disease markers in Canadian children and adolescents. We have demonstrated age- and sex-related differences in marker levels for lipids, insulin, and HOMA-IR that should be considered when evaluating these markers in children and adolescents.
Acknowledgements
The analysis presented in this paper was conducted at the Atlantic Research Data Centre, which is part of the Canadian Research Data Centre Network (CRDCN). The services and activities provided by the Atlantic Research Data Centre are made possible by the financial or in-kind support of the SSHRC, the CIHR, the CFI, Statistics Canada, and Dalhousie University. The views expressed in this paper do not necessarily represent the views of the CRDCN or its partners.
Funding
This work was supported by an IWK Health Centre (http://www.iwk.nshealth.ca) Establishment Grant awarded to Dr. Stefan Kuhle (FRN 09020). The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Availability of data and materials
The data that support the findings of this study are available from Statistics Canada through the Statistics Canada Research Data Centres program to researchers who meet the criteria for access to confidential data. The application process is described at http://www.statcan.gc.ca/eng/rdc/process
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In brief, researchers submit an application form and project proposal to the Statistics Canada Research Data Centres Program. Upon approval they have to undergo a security check. Once completed, they get access to one of the Research Data Centres in Canada to analyze the data. Only aggregated data can be released, and all output produced at the centres must be vetted by a Statistics Canada analyst before release.
Ethics approval and consent to participate
The Health Canada Research Ethics Board gave approval for the CHMS. All participants gave written informed consent; parents or guardians consented on behalf of children aged 6 to 13 years, and the child provided their assent to participate. The current project was approved by the IWK Health Centre Research Ethics Board, Halifax, NS, Canada (File # 1014413).
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
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Publisher’s Note
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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
