Prevalence, Risk Factors, and Clinical Characteristics of Lipodystrophy in Insulin-Treated Patients with Diabetes: An Old Problem in a New Era of Modern Insulin

Figures & data

Table 1 Demographic Data of Studied Participants (N=400)

	Total (N=400)	T1DM (N=56)	T2DM (N=344)
Age	65.6±15.4	45.2±13.7	68.9±12.9
Female	53.5%	48.2%	54.4%
Education
-Less than high school	156 (39.0%)	2 (3.6%)	154 (44.8%)
-High school	86 (21.5%)	9 (16.1%)	77 (22.4%)
-Bachelor degree or colledge	116 (29.0%)	32 (57.1%)	84 (24.4%)
-Higher than bachelor degree	42 (10.5%)	13 (23.2%)	29 (8.4%)
Duration of DM	23.0±10.2	20.1±11.6	23.5±9.8
Duration of insulin (years)	11.4±8.7	18.9±11.0	10.2±7.6
BMI (kg/m^2)	26.2±4.8	23.8±3.6	26.5±4.8
A1C (%NGSP)	7.9±1.6	7.8±1.5	7.9±1.6
Daily insulin dose (units/day)	41.9±24.9	46.5±17.8	41.1±25.8
Daily insulin dose (unit/kg/day)	0.6±0.3	0.7±0.3	0.6±0.3
Type of insulin*
Human insulin	150 (27.9%)	16 (24.6%)	134 (36.8%)
-Regular insulin	21	8	13
-NPH	15	4	11
-Pre-mixed human insulin	114	4	110
Insulin analog	387 (72.1%)	49 (75.4%)	230 (63.2%)
-Aspart	81	19	62
-Lispro	84	25	59
-Glulisine	18	4	14
-Glargine U100	96	19	77
-Glargine U300	31	5	26
-Detemir	9	2	7
-Degludec	68	17	51
Insulin device
-Insulin pen	375 (93.8%)	48 (85.7%)	327 (95.0%)
-Insulin syringe	20 (5.0%)	6 (10.7%)	14 (4.1%)
-Mixed (pen and syringe)	5 (1.2%)	2 (3.6%)	3 (0.9%)
Patients with concurrent anti-diabetic medications (%)	218 (54.5%)	11 (19.6%)	207 (60.2%)
Specified type of anti-diabetic medications^#
-Sulfonylurea	28	0	28
-Metformin	162	5	157
-DPP4 inhibitor	82	3	79
-Thiazolidinedione	58	2	56
-SGLT2 inhibitor	48	4	44
-GLP1 receptor agonist	12	0	12

Notes: *The denominator was 537, due to some patients using more than one type of insulin. ^#Some patients received more than one type of anti-diabetic medication.

Table 2 The Details of Insulin Regimens and Injection Techniques in Studied Participants

	Total (N=400)	T1DM (N=56)	T2DM (N=344)
Insulin regimen
Mixed split	155 (38.8%)	7 (12.5%)	148 (43.0%)
Basal bolus	87 (21.8%)	43 (76.8%)	44 (12.8%)
Basal plus	60 (15.0%)	5 (8.9%)	55 (16.0%)
Basal only	86 (21.4%)	–	86 (25.0%)
Others	12 (3.0%)	1 (1.8%)	11 (3.2%)
Location of injection site
Abdomen	371 (92.8%)	43 (76.8%)	328 (95.3%)
Thigh	4 (1.0%)	–	4 (1.2%)
Arm	1 (0.2%)	1 (1.8%)	–
Mixed	23 (5.8%)	11 (19.6%)	12(3.5%)
Hip	1 (0.2%)	1 (1.8%)	–
Rotation injection site
Yes	298 (74.5%)	41 (73.2%)	257 (74.7%)
No	102 (25.5%)	15 (26.8%)	87 (25.3%)
Needle length
4 mm	20 (5.0%)	2 (3.6%)	18(5.2%)
5 mm	82 (20.5%)	13 (23.2%)	69 (20.1%)
6 mm	200 (50.0%)	27 (48.2%)	173 (50.3%)
8 mm	93 (23.2%)	11 (19.6%)	82 (23.8%)
Others	5 (1.3%)	3 (5.4%)	2 (0.6%)
Reused insulin needles
Yes	378 (94.5%)	53 (94.6%)	325 (94.5%)
3 times	88 (23.3%)	13 (24.5%)	75 (23.1%)
4–5 times	87 (23.0%)	10 (18.9%)	77 (23.7%)
>5 times	203 (53.7%)	30 (56.6%)	173 (53.2%)
No	22 (5.5%)	3 (5.4%)	19 (5.5%)

Table 3 Comparison of Clinical Parameters and Glycemic Control in Patients with and without Insulin-Induced Lipohypertrophy

	Patients with LH (N=149)	Patients without LH (N=251)	P-value
Age	64.8±14.2	66.0±16.1	0.420
Female	71 (47.7%)	143 (57.0%)	0.071
Education			0.338
Less than high school	55 (37.2%)	101 (40.1%)
High school	31 (20.9%)	55 (21.8%)
Bachelor degree or colledge	50 (33.8%)	66 (26.2%)
Higher than bachelor degree	12 (8.1%)	30 (11.9%)
Durationof DM	24.1 ± 8.9	22.4 ± 10.8	0.103
Duration of insulin (years)	13.4 ± 9.2	10.3 ± 8.1	0.001
BMI (kg/m^2)	25.9 ± 4.8	26.3 ± 4.8	0.437
A1C (%NGSP)	7.8 ± 1.5	7.9 ± 1.7	0.545
Daily insulin dose (units/day)	43 ± 24	41 ± 25	0.439
Daily insulin dose (unit/kg/day)	0.6 ± 0.3	0.6 ± 0.3	0.441
Type of insulin			0.021
Human insulin	54 (36.2%)	59 (23.5%)
Insulin analog	88 (59.1%)	181 (72.1%)
Both types of insulin	7 (4.7%)	11 (4.4%)
Insulin device			0.265
Insulin pen	136 (91.3%)	239 (95.2%)
Insulin syringe	10 (6.7%)	10 (4.0%)
Mixed	3 (2.0%)	2 (0.8%)
Insulin regimen			0.074
Mixed split	61 (41.2%)	94 (37.3%)
Basal bolus	27 (18.2%)	60 (23.8%)
Basal plus	29 (19.6%)	31 (12.3%)
Basal only	29 (19.6%)	57 (22.6%)
Others	2 (1.4%)	10 (4.0%)
Location of injection site			0.282
Abdomen	143 (96.0%)	228 (90.8%)
Thigh	-	4 (1.6%)
Arm	-	1 (0.4%)
Mixed	6 (4.0%)	17 (6.8%)
Hip	-	1 (0.4%)
Rotation injection site			<0.001
Yes	60 (40.3%)	238 (94.8%)
No	88 (59.7%)	13 (5.2%)
Needle length			0.652
4 mm	5 (3.4%)	15 (6.0%)
5 mm	30 (20.1%)	52 (20.7%)
6 mm	75 (50.3%)	125 (49.8%)
8 mm	38 (25.5%)	55 (21.9%)
Others	1 (0.7%)	4 (1.6%)
Reused insulin needles			0.057
Yes	145 (97.3%)	233 (92.8%)
No	4 (2.7%)	18 (7.2%)

Table 4 Factors Associated with the Presence of Insulin-Induced Lipohypertrophy

Variables	Univariate			Multivariate
	OR	P-value	95% CI	OR	P-value	95% CI
T1DM	1.58	0.117	0.89–2.79
Female	0.67	0.057	0.45–1.01
Education less than high school	0.88	0.564	0.58–1.34
BMI <25 kg/m^2	1.24	0.293	0.83–1.87
Duration of insulin ≥10 years	1.79	0.006	1.19–2.70	1.83	0.025	1.08–3.09
Number of daily insulin injection	0.98	0.936	0.64–1.52
Use of human insulin	1.82	0.006	1.19–2.80	1.78	0.037	1.04–3.05
Insulin dose ≥0.6 units/kg/day	1.03	0.872	0.69–1.55
Incorrect insulin rotation	24.93	<0.001	13.27–46.86	26.14	<0.001	13.68–49.95
Use of needle length ≥8 mm	1.17	0.510	0.733–1.87
Reuse insulin needles	2.769	0.070	0.92–8.35
3 times	2.972	0.067	0.93–9.52
4–5 times	2.491	0.126	0.77–8.02
>5 times	2.808	0.071	0.92–8.60

Figure 1 (A) The overall prevalence of insulin-induced lipohypertrophy and prevalence stratified by type of diabetes and duration of insulin treatment. (B) The prevalence of insulin-induced lipohypertrophy in people with long-standing (≥10 years) DM and prevalence stratified by type of diabetes.

Figure 2 (A) A typical insulin-induced lipohypertrophy in T2DM patient with ultrasound characteristics of thickening heterogeneous echogenicity of subcutaneous fat. (B) Insulin-induced lipoatrophy in a patient with long-standing T2DM with ultrasonographic findings of lipoatrophy revealed a focal area of decreased thickness and increased heterogeneous echogenicity of subcutaneous fat texture. (C) A T1DM patient with suspected insulin-derived localized amyloidosis based on palpable subcutaneous mass at subumbilical region and homogeneous hypoechoic fat interspersed from ultrasound.

Figure 3 (A) Frequency of lipodystrophy checking from healthcare professions. (B) Self-checking the presence of lipodystrophy by patients.