Increased insulin sensitivity in individuals with neurofibromatosis type 1

Forty patients with NF1 were matched by sex, age, and body mass index (BMI) to 40 controls from the community. Blood samples were collected for biochemical assessment. Homeostasis model assessment adiponectin (HOMA-AD), Homeostasis model assessment insulin resistance (HOMA-IR), and adiponectin/leptin ratio (ALR) were used to identify IR.

Results

The median HOMA-IR values were similar between the groups. However, the HOMA-AD value was significantly lower and the ALR significantly higher in the NF1 group. Fasting blood glucose (FBG), leptin, and visfatin levels of patients with NF1 were significantly lower, although adiponectin levels were significantly higher than those in the controls. Fasting insulin and blood glucose levels 2 hours after administration of 75 g of dextrose, glycated hemoglobin, and resistin showed no significant differences between groups. The HOMA-AD correlated with BMI, FBG, blood glucose levels 2 hours after administration of 75 g of dextrose, fasting insulin, glycated hemoglobin, adiponectin, leptin, visfatin, ALR, and HOMA-IR. The ALR correlated with BMI leptin, visfatin, and adiponectin.

Conclusions

Lower levels of FBG, leptin, visfatin, and HOMA-AD, and higher adiponectin levels and ALR may be related to increased insulin sensitivity and lower occurrence of type 2 diabetes mellitus in patients with NF1

Keywords
Blood glucose; neurofibromatosis 1; diabetes mellitus; type 2; insulin resistance

Variables		NF1 (n = 40)	Controls (n = 40)	P-value
Sex^a a n (%);
	Female	28 (70.0)	28 (70.0)	1.000^d d McNemar's test;
	Male	12 (30.0)	12 (30.0)
Age^b b Mean (standard deviation);		40.7 (11.8)	40.4 (12.1)	0.390^e e Paired t-test;
Weight (kg)^b b Mean (standard deviation);		60.6 (13.1)	68.5 (14.5)	< 0.001
Height (m)^c c Median (percentiles 25-75);		1.57 (1.51–1.63)	1.62 (1.57–1.74)	< 0.001
BMI (kg/m²)^c c Median (percentiles 25-75);		24.2 (21.6–26.2)	24.6 (22.3–26.5)	0.096^f f Wilcoxon Test; BMI: body mass index.
Physical activity level^* * According to the International Physical Activity Questionnaire (25).
	Not active	9 (22.5)	14 (35)
	Not very active	3 (7.5)	5 (12.5)	0.343^d d McNemar's test;
	Moderately active	28 (70)	21 (52.5)

Variables		NF1 (n = 40)	Controls (n = 40)	P-value
HOMA-IR^a a Median (percentiles 25 and 75);		1.1 (0.7-1.6)	1.3 (0.9–2.3)	0.147^c c Wilcoxon test;
HOMA-AD^a a Median (percentiles 25 and 75);		1.0 (0.5–1.7)	1.9 (1.0–4.1)	0.001^c c Wilcoxon test;
ALR^a a Median (percentiles 25 and 75);		3.8 (2.1–12.6)	1.2 (0.7–2.1)	< 0.001^c c Wilcoxon test;
FBG (mg/dL)^a a Median (percentiles 25 and 75);		83.5 (78.0–90.0)	86.0 (83.0–94.0	0.008^c c Wilcoxon test;
FBG classification^b b n (%);
	Normal (< 100 mg/dL)	40 (100.0)	35 (87.5)	0.027^d d Fisher's exact test;
	Impaired (≥ 100 mg/dL)	0	5 (12.5)
Glucose level postdextrose administration (mg/dL)^a a Median (percentiles 25 and 75);		96.5 (85.3–112.5)	99.5 (88.0–118.3)	0.255^c c Wilcoxon test;
Glucose level postdextrose administration classification^b b n (%);
	Normal (< 140 mg/dL)	38 (95.0)	34 (85.0)	0.219^e e McNemar's test. HOMA-IR: Homeostasis Model Assessment Insulin Resistance; HOMA-AD: Homeostasis Model Assessment Adiponectin; FBG: fasting blood glucose; HbA1c: glycated hemoglobin; ALR: adiponectin-leptin ratio.
	Impaired (≥ 140 mg/dL)	2 (5.0)	6 (15.0)
HbA1c (%)^a a Median (percentiles 25 and 75);		5.2 (5.0–5.5)	5.4 (5.0–5.7)	0.100^c c Wilcoxon test;
HbA1c classification^b b n (%);
	< 5.7%	30 (75.0)	26 (65.0)
	5.7–6,4%	10 (25.0)	14 (35.0)	0.503^e e McNemar's test. HOMA-IR: Homeostasis Model Assessment Insulin Resistance; HOMA-AD: Homeostasis Model Assessment Adiponectin; FBG: fasting blood glucose; HbA1c: glycated hemoglobin; ALR: adiponectin-leptin ratio.
	≥ 6.5%	0	0
Fasting insulin (µU/mL)^a a Median (percentiles 25 and 75);		4.9 (3.6–11.6)	6.0 (4.4–15.7)	0.357^c c Wilcoxon test;
Adiponectin (µg/mL)^a a Median (percentiles 25 and 75);		23.7 (17.0–39.4)	15.3 (11.3–20.9	0.001^c c Wilcoxon test;
Leptin (ng/mL)^a a Median (percentiles 25 and 75);		5.7 (3.1–11.7)	11,9 (6.8–20.7)	0.042^c c Wilcoxon test;
Resistin (ng/mL)^a a Median (percentiles 25 and 75);		6.8 (3.4–9.0)	5,8 (2.4–9.8)	0.490^c c Wilcoxon test;
Visfatin (ng/mL)^a a Median (percentiles 25 and 75);		118.2 (105.8–124.8)	138.2 (125.5–147.7)	< 0.001^c c Wilcoxon test;

Variable	Correlation coefficient^a a Spearman correlation coefficient; FBG: fasting blood glucose; HbA1c: glycated hemoglobin; HOMA-IR: Homeostasis Model Assessment-Insulin Resistance; ALR: adiponectin-leptin ratio; HOMA-AD: Homeostasis Model Assessment-Adiponectin.	P-value
BMI	0.349	0.002
FBG	0.448	< 0.001
Fasting insulin	0.667	< 0.001
Post dextrose glucose	0.388	< 0.001
HbA1c	0.315	0.004
Adiponectin	-0.662	< 0.001
Leptin	0.300	0.007
Visfatin	0.269	0.016
ALR	-0.547	< 0.001
HOMA-IR	0.700	< 0.001

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[1] Correspondence to: Nilton Alves de Rezende, Centro de Referência de Neurofibromatose, Departamento de Medicina Interna, Universidade Federal de Minas Gerais Alameda Álvaro Celso, 55 30150-260 – Belo Horizonte, MG, Brasil narezende@terra.com