Substantial inter-individual variations in insulin secretion and sensitivity across the glucometabolic spectrum

Figures & data

Table 1. Clinical characteristics of subjects in Cohort I.

	All	Men	Women
	n = 486	n = 220	n = 266
Age (years)	54.5 ± 9.1	53.4 ± 9.8	55.5 ± 8.0
BMI (kg/m^2)	32.3 ± 4.4	32.0 ± 3.8	32.7 ± 4.4
Waist circumference (cm)	106.1 ± 11.8	110.9 ± 9.9	102.6 ± 10.5
Hip circumference (cm)	112.7 ± 10.0	110.0 ± 9.0	115.3 ± 10.2
Waist-hip-ratio	0.9 ± 0.1	1.0 ± 0.1	0.9 ± 0.1
Fat (kg)	33.2 ± 9.3	29.9 ± 8.5	36.0 ± 8.8
Body fat percentage (%)	36.5 ± 8.8	29.9 ± 5.6	41.9 ± 6.8
Fat free mass (kg)	56.6 ± 13.8	68.3 ± 10.2	47.3 ± 7.6
F-plasma glucose (mmol/L)	6.0 ± 0.8	6.0 ± 0.8	5.9 ± 0.8
F-TAG (mmol/L)^a	1.59 (1.17, 2.23)	1.63 (1.18, 2.23)	1.56 (1.17, 2.21)
F-HDL cholesterol (mmol/L)	1.10 ± 0.29	0.98 ± 0.22	1.20 ± 0.29
Systolic BP (mmHg)	139 ± 15	139 ± 14	138 ± 15
Diastolic BP (mmHg)	86 ± 9	88 ± 9	85 ± 9

BMI: body mass index; F: fasting; TAG: triglyceride; HDL: high-density lipoprotein; BP: blood pressure.

Data represent means ± SD.

^a Median (25% percentile, 75% percentile).

Table 2. Clinical characteristics of subjects in cohort II.

	All	Men	Women
	n = 62	n = 37	n = 25
Age (years)	55.7 ± 9.4	57.1 ± 9.2	53.5 ± 9.2
BMI (kg/m^2)	31.9 ± 4.9	31.1 ± 4.1	33.0 ± 5.7
Waist circumference (cm)	109.2 ± 12.4	110.2 ± 10.9	107.8 ± 14.2
Hip circumference (cm)	105.4 ± 9.3	104.3 ± 7.7	107.0 ± 11.1
Waist-hip-ratio	1.0 ± 0.1	1.1 ± 0.1	1.0 ± 0.1
Body fat percentage (%)	33.5 ± 8.3	28.2 ± 4.1	41.2 ± 6.7
Fat free mass (kg)	60.8 ± 12.6	68.3 ± 10.0	49.6 ± 6.4
HbA1c (mmol/mol)	62 ± 14	61 ± 14	63 ± 15
Diabetes duration (years)	10.0 ± 6.4	9.8 ± 6.9	10.2 ± 5.5
F-plasma glucose (mmol/L)	10.7 ± 3.3	10.4 ± 3.1	11.1 ± 3.6
F-TAG (mmol/L)^a	1.3 (0.9, 2.0)	1.3 (0.9, 2.0)	1.3 (0.9, 1.9)
F-HDL cholesterol (mmol/L)	1.0 ± 0.3	1.0 ± 0.2	1.1 ± 0.3
Systolic BP (mmHg)	128 ± 15	131 ± 14	122 ± 16
Diastolic BP (mmHg)	84 ± 9	86 ± 9	82 ± 9

BMI: body mass index; F: fasting; TAG: triglyceride; HDL: high-density lipoprotein; BP: blood pressure.

Data represent means ± SD.

^a Median (25% percentile, 75% percentile).

Figure 1. Individual data for insulin secretion. Measured as HOMA2-B in cohort I (A) and cohort II (B), and as iAUC_0–8 min in cohort I (C) and in cohort II (D). iAUC_0–8 min: incremental area under the curve for the first phase (0–8 min) insulin response to glucose.

Table 3. Variation in insulin secretion indices for subjects in cohorts I and II.

	Cohort I			Cohort II
	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a
HOMA2-B (%)	67–992	135–353	2.6	15–153	18–122	6.9
iAUC0–8 min (mU L^−1min^−1)	−60–3397	18–750	40.7	−263–1194	−75–882	11.8
DI^b	−89–4053	53–2330	37.0	−5238–43,818	−3416–31,188	9.1

^a Truncated range was calculated after exclusion of extreme values (<5th and >95th percentiles), and the fold variation calculated as the 95th percentile divided by the absolute value of the 5th percentile. DI: disposition index, iAUC_0–8 min: incremental area under the curve for the first phase (0–8 min) insulin response to glucose. ^bValues for DI in cohort I and II are not comparable due to different estimates of insulin sensitivity.

Figure 2. Individual data for insulin resistance. Measured as HOMA2-IR in cohort I (A) and cohort II (B), and as SI in cohort I (C) and as TGD in cohort II (D). HOMA2-IR: homeostatic model assessment for insulin resistance, SI: insulin sensitivity index; TGD: total glucose disposal.

Table 4. Variation in insulin resistance or insulin sensitivity indices for subjects in cohorts I and II.

	Cohort I			Cohort II
	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a
F-insulin (mU/L)	<2.5–42.7	4.0–20.5	5.1	3.3–138.3	4.7–38.0	8.1
F-C-peptide (pmol/L)	271–1987	350–1410	3.1	312–2289	513–1832	3.6
HOMA2-IR	2.3–8.9	3.1–8.3	2.6	0.8–5.6	1.5–4.9	3.3
SI ((mU/L)^−1min^−1)	0.19–15.29	0.86–5.85	6.8	NA	NA	NA
GIR (μmol kgFFM^−1 min^−1)	NA	NA	NA	1.2–76.3	5.6–50.6	9.0
TGD (μmol kgFFM^−1 min^−1)	NA	NA	NA	12.9–101.6	15.1–82.5	5.5

^a Truncated range was calculated after exclusion of extreme values (<5th and 95th percentiles), and fold variation calculated as the 95th percentile divided by the absolute value of the 5th percentile was the highest value divided by the lowest value after truncation. S_I: sensitivity index; GIR: glucose infusion rate; FFM: fat free mass; TGD: total glucose disposal; NA: not applicable.

Table 5. Variation in components of the metabolic syndrome for subjects in cohorts I and II.

	Cohort I			Cohort II
	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a	Variation	Variation in 5th and 95th percentiles	Fold variation 5th and 95th percentiles^a
F-glucose (mmol/L)	3.1–10.3	4.7–8.2	1.5	5.7–19.7	6.5–16.8	2.6
F-TAG (mmol/L)	0.42–7.11	0.82–3.35	4.1	0.6–4.7	0.7–3.3	4.7
HDL cholesterol (mmol/L)	0.47–2.33	0.72–1.59	2.2	0.7–1.9	0.7–1.5	2.1
Systolic BP (mmHg)	105–189	117–164	1.4	96–164	101–154	1.5
Diastolic BP (mmHg)	62–118	71–101	1.4	63–107	69–98	1.4
Waist circumference (cm)	70.0–174.7	88.0–127.7	1.4	79.3–39.5	92.4–126.9	1.4
BMI (kg/m^2)	21.1–45.3	25.5–40.0	1.5	21.8–42.0	25.4–40.3	1.6

^a Truncated range was calculated after exclusion of extreme values (<5th and >95th percentiles), and the fold variation calculated as the 95th percentile divided by the absolute value of the 5th percentile. TAG: triacylglycerol; HDL: high-density lipoprotein; BP: blood pressure; BMI: body mass index.

Figure 3. Relationship between insulin sensitivity (SI) and first-phase insulin secretion (iAUC) across different categories of fasting plasma glucose in cohort 1. Green points: subjects with fasting plasma glucose <5.6 mmol/L, orange points: subjects with fasting plasma glucose 5.6–7.0 mmol/L and red points: subjects with fasting plasma glucose >7.0 mmol/L. The green trend line shows the log-hyperbola relationship between insulin sensitivity and secretion within those with normal fasting plasma glucose. iAUC_0–8 min: incremental area under the curve for the first phase (0–8 min) insulin response to glucose.

Figure 4. Distribution of MetS patients (n = 486) according to k-means clustering. (A) Pairwise comparison of age, BMI, HOMA-B and HOMA-IR between patients in the identified four clusters. The comparison was made using ANOVA with Tukey HSD post hoc correction for multiple testing. (B) The optimal number of clusters was chosen using the elbow-method. (C) Clustering of patients according to k means and principal component analysis. ***p< .001, **p< .01 and *p< .05. N.S: not significant. Tot. SS: total within the sum of squares. Dim1/2 = principal component 1/2.