Fig. 1Fasting plasma levels of ghrelin (pmol/L) in subjects with type 2 diabetes mellitus (T2DM) and healthy non-diabetic controls from Saudi Arabia. Comparison between (A) all subjects with T2DM versus all control subjects, and (B) age- and sex-matched subjects with T2DM versus healthy subjects. Ghrelin levels were consistently significantly lower in patients with T2DM. The horizontal line within each box represents the median, while the lower and upper ends of the box are the 25th and 75th percentiles, the cap of the vertical line is the 95th percentile, and the closed circles are outliers.
Fig. 2Fasting plasma levels of ghrelin (pmol/L); comparison between (A) all study subjects (type 2 diabetes mellitus [T2DM] subjects and controls) with or without insulin resistance (IR) (homeostatic model assessment of insulin resistance [HOMA-IR] ≥3 and <3, respectively), (B) T2DM subjects with or without IR, and (C) T2DM subjects with moderate IR (HOMA-IR 3 to 5) and severe IR (HOMA-IR >5). Ghrelin levels were significantly lower in subjects with IR in (A) and (B) (P<0.001 and P=0.049, respectively). The horizontal line within each box represents the median, while the lower and upper ends of the box are the 25th and 75th percentiles, the cap of the vertical line is the 95th percentile, and the closed circles are outliers.
Table 1Age and Biochemical Profiles of the Study Population, Comprising Saudi Subjects with T2DM and Apparently Healthy Non-Diabetic Subjects
Parameter |
Control subject |
T2DM subject |
P value |
Samples from |
|
|
|
All subjects |
101 |
107 |
Ghrelin-measured |
68 |
97 |
Age-matched |
30 |
80 |
Age matched (ghrelin) |
24 |
71 |
Sex, male/female |
57/44 |
61/46 |
|
Disease duration, yr |
|
|
|
Mean±SD |
NA |
8.013±7.023 |
Median (interquartile range) |
NA |
6.0 (3.75–10.00) |
BMI, kg/m2
|
28.9 (25.5–32.4) |
32.5 (29.7–36.4) |
<0.001a
|
Weight, kg |
75.0 (65.6–88.2) |
85.0 (74.5–94.7) |
<0.001a
|
Family history of DM |
46/101 (45.5) |
74/107 (69.2) |
<0.001b
|
FBG level, mmol/L |
5.1 (4.9–5.4) |
7.8 (6.4–10.8) |
<0.001 |
HbA1c, mmol/mol |
37 (32–40) |
64 (52–74) |
<0.001 |
HbA1c, % |
5.5 (5.1–5.8) |
8.0 (6.9–8.9) |
- |
FBI level, pmol/L |
49.0 (35.0–58.3) |
59.0 (38.5–89.4) |
0.006 |
FBI (age-matched), pmol/L |
42.5 (36.0–58.0) |
60.9 (40.1–99.5) |
0.009 |
C-peptide, ng/mL |
1.91 (1.43–2.54) |
2.23 (1.49–2.92) |
0.105 |
HOMA-IR (all subjects) |
1.53 (1.09–1.96) |
2.90 (1.80–5.29) |
<0.001 |
HOMA-IR (age-matched) |
1.5 (1.1–2.0) |
3.35 (2.25–5.90) |
<0.001 |
Table 2Biochemical Profile of IR and Non-IR Healthy Subjects and T2DM Subjects from Saudi Arabia
Parameter |
Control subjects (n=101) |
T2DM subjects (n=107) |
IR (HOMA-IR ≥3) |
Non-IR (HOMA-IR <3) |
P valuea
|
IR (HOMA-IR ≥3) |
Non-IR (HOMA-IR <3) |
P valuea
|
Subject |
6 (5.9) |
95 (94.1) |
|
50 (46.7)b
|
57 (53.3) |
|
Age, yr |
34.5 (34.0–47.0) |
35.0 (28.0–43.0) |
0.499 |
48.8±9.8 |
48.2±11.8 |
0.769 |
Ghrelin level, pmol/L |
17.2 (14.8–22.6) (n=5) |
19.3 (14.9–23.6) (n=63) |
0.823 |
10.4 (7.1–16.9) (n=42) |
14.5 (11.1–16.5) (n=55) |
0.049 |
BMI, kg/m2
|
38.40±4.50 |
28.79±5.43 |
<0.001 |
34.1 (31.3–39.5) |
31.2 (28.1–33.0) |
<0.001 |
Weight, kg |
102.2±16.24 |
75.39±15.49 |
<0.001 |
90.535±19.12 |
81.893±15.15 |
0.011 |
FBG level, mmol/L |
5.1 (5.1–5.2) |
5.1 (4.9–5.4) |
0.840 |
9.8 (7.0–12.70) |
7.1 (6.1–9.3) |
<0.001 |
HbA1c, mmol/mol |
37.7 (36.6–41.0) |
36.6 (32.2–39.9) |
- |
70.5 (59.6–83.6) |
55.2 (46.4–67.8) |
|
HbA1c, % |
5.6 (5.5–5.9) |
5.5 (5.1–5.8) |
0.489 |
8.6 (7.6–9.8) |
7.2 (6.4–8.35) |
<0.001 |
C-peptide, ng/mL |
4.17±0.83 |
1.98±0.781 |
<0.001c
|
2.34 (1.38–3.63) |
2.03 (1.55–2.62) |
0.130 |
FBI, pmol/L |
111.3±19.45 |
46.86±17.67 |
<0.001c
|
94.3 (74.0–161.0) |
40.2 (27.4–51.5) |
<0.001 |
HOMA-IR |
3.42 (3.19–3.48) |
1.51 (1.08–1.77) |
<0.001 |
5.35 (4.05–8.25) |
1.83 (1.21–2.38) |
<0.001 |
Table 3Correlations of the HOMA-IR Index with Age, Disease Duration, and Anthropometric and Glycemic Parameters in Saudis (Healthy Subjects and Patients with IR and Non-IR T2DM)
Variable |
HOMA-IR vs. Control subjects |
HOMA-IR vs. T2DM subjects (all) |
Non-IR-T2DM |
IR-T2DM |
Age |
R=0.008, P=0.935 (n=101) |
R=–0.114, P=0.244 (n=107) |
R=0.062, P=0.647 (n=57) |
R=–0.211, P=0.141 (n=50) |
Disease duration |
- |
R=0.065, P=0.526 (n=97) |
R=–0.104, P=0.472 (n=50) |
R=0.027, P=0.859 (n=47) |
BMI |
R=0.432, P<0.001 (n=97) |
R=–0.0409, P=0.680 (n=104) |
R=0.104, P=0.447 (n=56) |
R=–0.180, P=0.222 (n=48) |
Weight |
R=0.422, P<0.001 (n=99) |
R=–0.070, P=0.478 (n=105) |
R=0.042, P=0.759 (n=56) |
R=–0.196, P=0.178 (n=49) |
FBG |
R=0.223, P=0.025 (n=101) |
R=0.133, P=0.171 |
R=0.118, P=0.381 (n=57) |
R=0.063, P=0.665 (n=50) |
HbA1c |
R=–0.037, P=0.714 (n=101) |
R=0.123, P=0.206 |
R=–0.089, P=0.510 (n=57) |
R=0.026, P=0.860 (n=50) |
FBI |
R=0.979, P<0.001 (n=101) |
R=0.991, P<0.001 |
R=0.774, P<0.001 (n=57) |
R=0.990, P<0.001 (n=50) |
C-peptide |
R=0.718, P<0.001 (n=101) |
R=–0.087, P=0.372 |
R=0.287, P=0.031 (n=57) |
R=–0.187, P=0.194 (n=50) |
Table 4Correlations of Plasma Ghrelin Levels with Anthropometric and Glycemic Parameters and the HOMA-IR Index in Saudi Subjects (Healthy and Patients with T2DM: All and with IR Only)
Variable |
Ghrelin vs. |
Control subjects |
Total T2DM subjects |
T2DM subjects with IR |
Age |
R=0.038, P=0.762 (n=68) |
R=–0.028, P=0.789 (n=97) |
R=–0.002, P=0.992 (n=42) |
Duration |
NA |
R=0.194, P=0.068 (n=89) |
R=0.177, P=0.276 (n=40) |
BMI |
R=–0.077, P=0.544 (n=64) |
R=–0.120, P=0.249 (n=95) |
R=0.084, P=0.604 (n=41) |
Weight |
R=–0.255, P=0.039 (n=66) |
R=–0.255, P=0.012 (n=96) |
R=–0.149, P=0.347 (n=42) |
FBG |
R=–0.038, P=0.761 (n=68) |
R=–0.0658, P=0.522 (n=97) |
R=–0.069, P=0.666 (n=42) |
HbA1c |
R=0.215, P=0.078 (n=68) |
R=–0.0449, P=0.662 (n=97) |
R=0.020, P=0.898 (n=42) |
FBI |
R=–0.312, P=0.010 (n=68) |
R=–0.192, P=0.059 (n=97) |
R=–0.217, P=0.168 (n=42) |
C-peptide |
R=–0.217, P=0.076 (n=68) |
R=–0.0155, P=0.880 (n=97) |
R=0.027, P=0.867 (n=42) |
HOMA-IR |
R=–0.303, P=0.012 (n=68) |
R=–0.195, P=0.055 (n=97) |
R=–0.224, P=0.154 (n=42) |