Interactions between ghrelin, leptin and IGF-I affect metabolic syndrome and early atherosclerosis

Figures & data

Table

ANOVA	analysis of variance
ANCOVA	analysis of covariance
HDL	high-density lipoprotein
IDF	International Diabetes Federation
IGF-I	insulin-like growth factor I
IMT	intima-media thickness
MS	metabolic syndrome
OR	odds ratio
OPERA	Oulu Project Elucidating Risk of Atherosclerosis
RIA	radioimmunoassay
VLDL	very-low-density lipoprotein

Table I.  Main characteristics of the control and hypertensive cohorts by gender. Values are means (SD) or percentages.

	Control cohort			Hypertensive cohort
	Men (n=259)	Women (n=267)	All (n=526)	Men (n=261)	Women (n=258)	All (n=519)
Age (years)	50.9 (6.1)	51.8 (6.0)	51.4 (6.0)	50.5 (5.9)	51.8 (5.9)	51.2 (5.9)
Type 2 diabetes (%)^a	5.0	3.4	4.2	14.9^b	12.4^b	13.7^b
BMI (kg/m^2)	26.5 (3.5)	26.2 (4.4)	26.4 (4.0)	29.4 (4.4)^b	28.7 (5.3)^b	29.0 (4.9)^b
Systolic BP (mmHg)	145 (20)	137 (21)	141 (21)	158 (21)^b	152 (21)^b	155 (21)^b
Diastolic BP (mmHg)	88 (10)	82 (12)	85 (12)	97 (10)^b	90 (11)^b	94 (11)^b
Smoking (pack years)	17.1 (14.6)	7.8 (12.4)	12.4 (14.3)	15.4 (13.9)	7.6 (12.3)	11.5 (13.7)
Alcohol consumption (g/week)	90 (100)	23 (36)	56 (82)	106 (126)	31 (48)	68 (103)
Fasting glucose (mmol/L)	4.6 (1.1)	4.3 (0.6)	4.5 (0.9)	5.1 (1.9)^b	4.9 (1.8)^b	5.0 (1.9)^b
Fasting insulin (mmol/L)	13.2 (12.2)	9.7 (6.2)	11.4 (9.8)	17.9 (12.9)^b	13.8 (10.3)^b	15.9 (11.8)^b
QUICKI	0.60 (0.09)	0.67 (0.12)	0.63 (0.11)	0.55 (0.10)^b	0.60 (0.13)^b	0.58 (0.12)^b
Total cholesterol (mmol/L)	5.8 (1.1)	5.5 (1.0)	5.6 (1.1)	5.8 (1.0)	5.7 (1.1)^b	5.8 (1.0)
LDL cholesterol (mmol/L)	3.7 (1.0)	3.3 (0.9)	3.5 (1.0)	3.6 (0.9)	3.5 (0.9)	3.5 (0.9)
HDL cholesterol (mmol/L)	1.2 (0.3)	1.6 (0.4)	1.4 (0.4)	1.2 (0.3)^b	1.4 (0.4)^b	1.3 (0.4)^b
Triglycerides (mmol/L)	1.6 (0.8)	1.2 (0.7)	1.4 (0.8)	2.0 (1.3)^b	1.6 (1.1)^b	1.8 (1.2)^b
IGF-I (ng/mL)	90 (41)	81 (39)	85 (40)	61 (36)^b	89 (53)	75 (47)^b
Ghrelin (pg/mL)	646 (230)	702 (237)	674 (235)	668 (266)	654 (234)^b	661 (250)
Leptin (ng/mL)	5.1 (3.1)	12.8 (7.3)	9.3 (6.9)	7.0 (4.1)^b	16.7 (10.1)^b	11.8 (9.1)^b

^aBased on World Health Organization criteria.

^bP<0.05 between hypertensive and control cohorts.

BMI = body mass index; BP = blood pressure; HDL = high-density lipoprotein; IGF-I = insulin-like growth factor I; LDL = low-density lipoprotein.

Table II.  Use of selected medications among the hypertensive and control cohorts by gender. Data are n (%).

	Control cohort			Hypertensive cohort
Medication	Men (n=259)	Women (n=267)	All (n=526)	Men (n=261)	Women (n=258)	All (n=519)
Antihypertensive medication	26 (10.0)	29 (10.9)	55 (10.5)	239 (91.6)	248 (96.1)	487 (93.8)
Diuretics	2 (0.8)	9 (3.4)	11 (2.1)	61 (23.4)	100 (38.8)	161 (31.0)
Beta-blockers	19 (7.3)	11 (4.1)	30 (5.7)	132 (50.6)	124 (48.1)	256 (49.3)
Calcium channel blockers	9 (3.5)	8 (3.0)	17 (3.2)	53 (20.3)	58 (22.5)	111 (21.4)
ACE inhibitors	4 (1.5)	7 (2.6)	11 (2.1)	106 (40.6)	87 (33.7)	193 (37.2)
Others	0	0	0	13 (5.0)	18 (7.0)	31 (6.0)
Lipid-lowering medication	6 (2.3)	4 (1.5)	10 (1.9)	13 (5.0)	7 (2.7)	20 (3.9)
Acetylsalicylic acid	12 (4.6)	6 (2.2)	18 (3.4)	25 (9.6)	15 (5.8)	40 (7.7)
Oral antidiabetic medication	2 (0.8)	2 (0.7)	4 (0.8)	10 (3.8)	9 (3.5)	19 (3.7)
Insulin	2 (0.8)	0	2 (0.4)	6 (2.3)	5 (1.9)	11 (2.1)
Hormone replacement therapy		60 (22.5)			48 (18.6)

ACE = angiotensin-converting enzyme.

Figure 1.  Fasting plasma ghrelin concentrations (adjusted for age and sex) in subjects with the metabolic syndrome (MS) compared to those without in the leptin quartiles. Mean leptin levels (ng/mL) in leptin quartiles (95% confidence intervals) are: I: 3.5 (3.0–4.0); II: 6.6 (6.0–7.1); III: 10.6 (10.1–11.1); IV: 21.9 (21.3–22.4). Standard deviations for ghrelin levels varied from 205 to 249 pg/mL.

Figure 2.  Fasting plasma ghrelin concentrations of the study subjects in relation to the number of International Diabetes Federation criteria of the metabolic syndrome (MS) met in leptin quartiles. Standard deviations for ghrelin levels varied from 176 to 333 pg/mL.

Figure 3.  Odds ratios with 95% confidence intervals of ghrelin quartile for type 2 diabetes (the fourth ghrelin quartile is used as a reference category) obtained by logistic regression analysis adjusted for age and sex in the highest leptin quartile. Mean ghrelin levels in ghrelin quartiles (pg/mL) (95% confidence intervals) are: I: 376.6 (364.0–389.2); II: 574.3 (561.7–586.8); III: 743.8 (731.2–756.3); IV: 975.8 (963.2–988.3).

Figure 4.  Adjusted (age, sex, smoking, systolic blood pressure, LDL-cholesterol and study group) means for ghrelin-leptin relation in different intima-media thickness (IMT) quartiles. Mean IMT values (mm) in IMT quartiles (95% confidence intervals) are: I: 0.69 (0.68–0.70); II: 0.77 (0.76–0.78); III: 0.84 (0.83–0.85); IV: 1.02 (1.02–1.03). Standard deviations for mean ghrelin-leptin relation varied from 72 to 133.

Figure 5.  Mean intima-media thickness (IMT) (logarithmically transformed) of carotid arteries in relation to ghrelin and insulin-like growth factor I (IGF-I) quartiles. Mean IGF-I levels (ng/mL) in IGF-I quartiles (95% confidence intervals) are: I: 29.2 (27.1–31.3); II: 60.7 (58.6–62.9); III: 89.3 (87.1–91.5); IV: 139.4 (137.3–141.6). Standard deviations for mean IMT levels varied from 0.05 to 0.75.