J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 13, Number 12, December 2021, pages 541-548

Hyperferritinemia Is a Predictor of Onset of Diabetes in Japanese Males Independently of Decreased Renal Function and Fatty Liver: A Fifteen-Year Follow-Up Study

Figure 2. Changes in HOMA-R and HOMA-β. HOMA-β decreased from the baseline level in group H, but HOMA-R did not differ between the two groups. Error bars show standard deviation of means. Statistical significance is performed by paired Student’s t-test.

Figure 3. Kaplan-Meier analysis showed a significant increase in the rate of T2D onset in the group with serum ferritin levels > 190 ng/mL (group H). Significant onset of diabetes in group H was observed at 5, 10 and 15 years, with odds ratios of 6.9 (2.2 - 21.9) (P < 0.01), 4.2 (1.6 - 11.5) (P < 0.01) and 4.3 (1.8 - 10.7) (P < 0.01), respectively. T2D: type 2 diabetes.

**Table 1.** Baseline Characteristics of Subjects With and Without New-Onset T2D in 15 Years
Parameter	Total	Incident T2D	P value
Values are means ± SD. T2D: type 2 diabetes; SD: standard deviation; FPG: fasting plasma glucose; PPG: postprandial glucose; HbA1c: hemoglobin A1c; IRI: immunoreactive insulin; CPR: C-peptide immunoreactivity; eGFR: estimated glomerular filtration rate. HOMA-R = FPG × IRI/405; HOMA-β = IRI × 360/(FPG - 63).
N	150	122	28
Age (years)	53.6 ± 8.3	53.4 ± 8.4	54.6 ± 8.1	0.492
Obesity, n (%)	54 (36%)	35 (29%)	19 (68%)	< 0.001
Hypertension, n (%)	19 (13%)	14 (11%)	5 (18%)	0.354
Dyslipidemia, n (%)	78 (52%)	59 (48%)	19 (68%)	0.092
Smoking habit, n (%)	62 (41%)	49 (40%)	13 (46%)	0.671
FPG (mg/dL)	97.3 ± 8.6	95.4 ± 7.3	105.6 ± 9.2	< 0.001
PPG (mg/dL)	143.7 ± 28.2	140.5 ± 27.9	157.9 ± 25.1	0.003
HbA1c (%)	5.71 ± 0.35	5.64 ± 0.34	6.01 ± 0.21	< 0.001
HOMA-R	1.28 ± 0.81	1.13 ± 0.73	1.92 ± 0.82	< 0.001
HOMA-β	54.0 ± 24.8	52.2 ± 24.5	62.1 ± 25.1	0.057
IRI (µU/mL)	5.19 ± 2.93	4.71 ± 2.72	7.29 ± 2.95	< 0.001
CPR (ng/mL)	1.88 ± 1.55	1.50 ± 0.61	3.40 ± 2.84	< 0.001
eGFR (mL/min/1.73 m²)	76.6 ± 12.3	77.8 ± 12.1	71.0 ± 11.8	0.008
Fatty liver	47 (31%)	30 (25%)	17 (61%)	< 0.001
Hemoglobin (g/dL)	14.9 ± 1.1	15.0 ± 1.1	14.8 ± 1.3	0.650

Table 1. Baseline Characteristics of Subjects With and Without New-Onset T2D in 15 Years

Parameter

Total

Incident T2D

P value

Yes

Values are means ± SD. T2D: type 2 diabetes; SD: standard deviation; FPG: fasting plasma glucose; PPG: postprandial glucose; HbA1c: hemoglobin A1c; IRI: immunoreactive insulin; CPR: C-peptide immunoreactivity; eGFR: estimated glomerular filtration rate. HOMA-R = FPG × IRI/405; HOMA-β = IRI × 360/(FPG - 63).

150

122

Age (years)

53.6 ± 8.3

53.4 ± 8.4

54.6 ± 8.1

0.492

Obesity, n (%)

54 (36%)

35 (29%)

19 (68%)

< 0.001

Hypertension, n (%)

19 (13%)

14 (11%)

5 (18%)

0.354

Dyslipidemia, n (%)

78 (52%)

59 (48%)

19 (68%)

0.092

Smoking habit, n (%)

62 (41%)

49 (40%)

13 (46%)

0.671

FPG (mg/dL)

97.3 ± 8.6

95.4 ± 7.3

105.6 ± 9.2

< 0.001

PPG (mg/dL)

143.7 ± 28.2

140.5 ± 27.9

157.9 ± 25.1

0.003

HbA1c (%)

5.71 ± 0.35

5.64 ± 0.34

6.01 ± 0.21

< 0.001

HOMA-R

1.28 ± 0.81

1.13 ± 0.73

1.92 ± 0.82

< 0.001

HOMA-β

54.0 ± 24.8

52.2 ± 24.5

62.1 ± 25.1

0.057

IRI (µU/mL)

5.19 ± 2.93

4.71 ± 2.72

7.29 ± 2.95

< 0.001

CPR (ng/mL)

1.88 ± 1.55

1.50 ± 0.61

3.40 ± 2.84

< 0.001

eGFR (mL/min/1.73 m²)

76.6 ± 12.3

77.8 ± 12.1

71.0 ± 11.8

0.008

Fatty liver

47 (31%)

30 (25%)

17 (61%)

< 0.001

Hemoglobin (g/dL)

14.9 ± 1.1

15.0 ± 1.1

14.8 ± 1.3

0.650

**Table 2.** Hazard Ratios for Incidence of Type 2 Diabetes in Univariate and Multivariate Analyses Using a Fine-Gray Model
Variables	Univariate, HR (95% CI)	P value	Multivariate, aHR (95% CI)	P value
HR: hazard ratio; CI: confidence interval; aHR: adjusted hazard ratio; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; TG: triglycerides; HDL: high-density lipoprotein; LDL: low-density lipoprotein; eGFR: estimated glomerular filtration rate; CRP: C-reactive protein; ALT: alanine transaminase.
BMI ≥ 25 kg/m²	4.28 (1.92 - 9.52)	< 0.001	1.14 (0.41 - 3.13)	0.80
SBP ≥ 130 mm Hg	2.58 (1.23 - 5.43)	0.012	1.61 (0.64 - 4.09)	0.32
DBP ≥ 85 mm Hg	2.89 (1.32 - 6.30)	0.008	1.37 (0.60 - 3.09)	0.45
TG ≥ 150 mg/dL	2.42 (1.15 - 5.08)	0.020	1.15 (0.45 - 2.95)	0.77
HDL < 40 mg/dL	2.48 (1.08 - 5.67)	0.031	2.40 (1.03 - 5.57)	0.04
LDL ≥ 140 mg/dL	1.35 (0.60 - 3.01)	0.470
eGFR < 70 mL/min/1.73 m²	4.30 (2.03 - 9.14)	< 0.001	2.75 (1.05 - 7.20)	0.04
Fatty liver	4.38 (2.06 - 9.30)	< 0.001	3.06 (1.23 - 7.61)	0.02
Uric acid ≥ 7.0 mg/dL	1.56 (0.71 - 3.41)	0.270
CRP ≥ 0.1 mg/dL	2.36 (1.13 - 4.91)	0.022	1.07 (0.44 - 2.58)	0.88
ALT ≥ 50 U/L	1.78 (0.66 - 4.76)	0.250
Ferritin > 190 ng/mL	3.97 (1.87 - 8.41)	< 0.001	2.77 (1.13 - 6.80)	0.03

Table 2. Hazard Ratios for Incidence of Type 2 Diabetes in Univariate and Multivariate Analyses Using a Fine-Gray Model

Variables

Univariate, HR (95% CI)

P value

Multivariate, aHR (95% CI)

P value

HR: hazard ratio; CI: confidence interval; aHR: adjusted hazard ratio; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; TG: triglycerides; HDL: high-density lipoprotein; LDL: low-density lipoprotein; eGFR: estimated glomerular filtration rate; CRP: C-reactive protein; ALT: alanine transaminase.

BMI ≥ 25 kg/m²

4.28 (1.92 - 9.52)

< 0.001

1.14 (0.41 - 3.13)

0.80

SBP ≥ 130 mm Hg

2.58 (1.23 - 5.43)

0.012

1.61 (0.64 - 4.09)

0.32

DBP ≥ 85 mm Hg

2.89 (1.32 - 6.30)

0.008

1.37 (0.60 - 3.09)

0.45

TG ≥ 150 mg/dL

2.42 (1.15 - 5.08)

0.020

1.15 (0.45 - 2.95)

0.77

HDL < 40 mg/dL

2.48 (1.08 - 5.67)

0.031

2.40 (1.03 - 5.57)

0.04

LDL ≥ 140 mg/dL

1.35 (0.60 - 3.01)

0.470

eGFR < 70 mL/min/1.73 m²

4.30 (2.03 - 9.14)

< 0.001

2.75 (1.05 - 7.20)

0.04

Fatty liver

4.38 (2.06 - 9.30)

< 0.001

3.06 (1.23 - 7.61)

0.02

Uric acid ≥ 7.0 mg/dL

1.56 (0.71 - 3.41)

0.270

CRP ≥ 0.1 mg/dL

2.36 (1.13 - 4.91)

0.022

1.07 (0.44 - 2.58)

0.88

ALT ≥ 50 U/L

1.78 (0.66 - 4.76)

0.250

Ferritin > 190 ng/mL

3.97 (1.87 - 8.41)

< 0.001

2.77 (1.13 - 6.80)

0.03