Gender Differences in Prevalence and Clinical Correlates of Lipohypertrophy in Insulin-Exposed Patients with Diabetes Mellitus

Figures & data

Table 1 Summary of Included Studies

Author (Year), Country	Study Population	Sample Population		Mean Diabetes Duration (Years, SD)	Mean Duration of Insulin use (Years, SD)	Detection Method(s),	BMI	HbA1c (%)
		Sample	Type of Diabetes
Lin et al (2021)^Citation19	Adult diabetes	Size: n=120 Mean age (years, SD): 59.21 ± 11.44 Gender (M/F): 50/70	T1DM: 120 T2DM: 0	ND	6.56 ± 4.26	Detection Observation, palpation, ultrasound examination	24.93 ± 3.18	9.45 ± 1.85%
Arora et al (2021)^Citation20	Adult diabetes	Size: n=500 Mean age (years, SD): 45.2 ± 16.5 Gender (M/F): 272/228	T1DM: 113 T2DM: 356 Pancreatic DM: 31	26.8 ± 6.9	3 (2.5–5.0)	Palpation, ultrasound examination	<18.5: 88 (17.6) 18.5–23.5: 192 (38.4) ≥23.5220 (44.0)	Mean: 9.9 ± 1.9 LH: 10.53 ± 1.73 No LH: 8.953 ± 0.5281
Gentile et al (2021)^Citation21	Adult diabetes	Size: n=780 Mean age (years, SD): 62 ± 15 Gender (M/F): 387/393	T1DM: 224 T2DM: 556	18 ± 11	10.1 ± 2.11	Palpation	29 ± 6	7.8 ± 1.3
Thewjitcharoen et al (2020)^Citation22	Adult diabetes	Size: n=400 Mean age (years, SD): 65.6 ± 15.4 Gender (M/F): 186/214	T1DM: 56 T2DM: 344	Mean: 23.0 ± 10.2 LH: 20.1 ± 11.6 No LH: 23.5 ± 9.8	Mean: 11.4 ± 8.7 LH: 18.9 ± 11.0 No LH: 10.2 ± 7.6	Palpation	Mean: 26.2 ± 4.8 LH: 23.8 ± 3.6 No LH: 26.5 ± 4.8	Mean: 7.9 ± 1.6 LH: 7.8 ± 1.5 No LH: 7.9 ± 1.6
Gentile et al (2020)^Citation12	Adult diabetes	Size: n=1227 Mean age (years, SD): 50.1 ± 10.5 Gender (M/F): ND	T1DM: 0 T2DM: 1227	26.8 ± 6.9	Age≤65: 8 ± 4 Age >65: 12 ± 5	Palpation, ultrasound examination	Age≤65: 8 ± 4 Age >65: 12 ± 5	Age≤65: 8.1 ± 1.2 Age >65: 8.9 ± 1.4
Lian et al (2018)^Citation23	Adult diabetes	Size: n=300 Mean age (years, SD): Male: 48.00 ± 3.0 Femal: 47.0 ± 4.0 Gender (M/F): 148/152	T1DM: ND T2DM: ND	LH: 10.98 ± 3.12 No LH: 7.24 ± 3.53	LH: 4.47 ± 3.12 No LH: 7.24 ± 3.53	Palpation, ultrasound examination	ND	ND
Tsadik et al (2018)^Citation24	Adult diabetes	Size: n=176 Mean age (years, SD): 51.36 ± 3.96 Gender (M/F): 86/90	T1DM: 176 T2DM: 0	ND	1–5: 65/46 >5: 38/27	Observation and the palpation	Underweight: 14/14 Healthy weight: 78/52 Obese: 6/4	ND
Hernar et al (2017)^Citation17	Adult diabetes	Size: n=215 Mean age (years, SD): 36.0 (18–82) Gender (M/F): 111/104	T1DM: 215 T2DM: 0	17.0 (1–57)	ND	Observation and the palpation	ND	8.0 (5.5–14.0)
Al Hayek et al (2016)^Citation25	Adult diabetes	Size: n=174 Mean age (years, SD): 55.43 ± 1.97 Gender (M/F): 90/84	T1DM: 174 T2DM: 0	6.1 ± 4.5	ND	Observation and the palpation	ND	ND
Sawatkar et al (2014)^Citation26	Adult diabetes	Size: n=500 Mean age (years, SD): 26.9 ± 6.9 Gender (M/F): 272/228	T1DM: 500 T2DM: 0	4.43 ± 4.4	12.51 ± 6.68	Observation and the palpation	19.2 ± 5.4	9.72 ± 3.0
Singha et al (2021)^Citation27	Juvenile diabetes	Size: n=91 Mean age (years, SD): 13.3 ± 4.1 Gender (M/F): 34/57	T1DM: 91 T2DM: 0	LH: 5.3 ± 2.7 No LH: 5.5 ± 2.8	ND	Observation and the palpation	ND	LH: 9.0 ± 2.6 No LH: 7.7 ± 1.1
McCann et al (2019)^Citation28	Juvenile diabetes	Size: n=76 Mean age (years, SD): 4–18 Gender (M/F): ND	T1DM: 76 T2DM: 0	<4: 43%LH >4: 57%LH	ND	Observation and the palpation	ND	ND
Magdy et al (2011)^Citation33	Juvenile diabetes	Size: n=119 Mean age (years, SD): 2 months to 21 Years Gender (M/F): 64/55	T1DM: 119 T2DM: 0	4.13 ± 3.67	ND	Observation and the palpation	ND	Normal: 76.1% Overweight: 15.0% Obese: 3.5% under weight: 5.3%
Conwell et al (2008)^Citation29	Juvenile diabetes	Size: n=50 Mean age (years, SD): 13.3 ± 3.5 Gender (M/F): 24/26	T1DM: 50 T2DM: 0	6.5 ± 3.7	2.8 ± 1.7	Observation and the palpation	21.6 ± 4.8	7.7 ± 1.1
Lombardo et al (2022)^Citation37	Juvenile diabetes	Size: n=212 Mean age (years, SD): 11.9 ± 4.7 Gender (M/F): 123/89	T1DM: 212 T2DM: 0	4.8 ± 3.4	ND	Inspection and palpation	ND	6.8 ± 1.6
Yan et al (2021)^Citation30	Mixed juvenile and Adult diabetes	Size: n=142 Mean age (years, SD): ≤18: 43/8 >18: 60/31 Gender (M/F): 82/60	T1DM: ND T2DM: ND	ND	LH: 4 (3, 7) No LH: 5 (3,7)	Observation and the palpation	LH: 20.56 (17.89, 23.0) No LH: 21.48 (20.06,22.6)	ND
Barola et al (2018)^Citation31	Mixed juvenile and Adult diabetes	Size: n=372 Mean age (years, SD): 17.1 (5.0–50.6) Gender (M/F): 204/168	T1DM: 372 T2DM: 0	5.6 ± 5.3	Mean: 7.9 ± 1.6 LH: 7.8 ± 1.5 No LH: 7.9 ± 1.6	Observation and the palpation	ND	Mean: 9.7 ± 2.6 LH: 10.0 ± 2.7 No LH: 9.2 ± 2.4
Gupta et al (2018)^Citation32	Mixed juvenile and Adult diabetes	Size: n=139 Mean age (years, SD): 21.71 ± 11.78 <18: 11.73 ± 3.96 ≥18: 25.51 ± 9.79 Gender (M/F): 75/64	T1DM: 139 T2DM: 0	8.70 ± 7.52	ND	Observation and the palpation	19.90 ± 4.68	9.71 ± 2.29
Blanco et al (2013)^Citation9	Mixed juvenile and Adult diabetes	Size: n=430 Mean age (years, SD): 49.0 ± 22.8 Gender (M/F): 221/202	T1DM: 177 T2DM: 253	ND	ND	Observation and the palpation	ND	ND
Vardar et al (2007)^Citation34	Mixed juvenile and Adult diabetes	Size: n=215 Mean age (years, SD): ND Gender (M/F): 137/78	T1DM: 31 T2DM: 184	26.8 ± 6.9	0–5 years: 66 (30.7%) 6–10 years: 59 (27.4%) 11–15 years: 57 (26.5%) 16–20 years: 33 (15.4%)	Observation and the palpation	Normal: 72 (33.5%) Overweight: 86 (40%) Obese: 57 (26.5%)

Abbreviation: ND, not detected.

Figure 1 PRISMA flowchart for inclusion of selected articles in this systematic review.

Note: PRISMA figure adapted from Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. Creative Commons.¹⁴

Table 2 Gender Differences in the Prevalence, Demographic and Clinical Features of LH in DM Patients (Adult DM)

Author (Year)	Male			Female			All				P-value
	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	Overall	LH Prevalence (%)
Lin et al (2021)^Citation19	48(57.83%)	22(59.46%)	68.57%	35(42.17%)	15(40.54%)	70.00%	83(69.17%)	37(30.83%)	120	69.17%	0.8673
Arora et l. (2021)^Citation20	151(52.07%)	272(54.40%)	55.51%	139(47.93%)	228(45.60%)	60.96%	290(58.00%)	210(42.00%)	500	58.00%	0.2188
Gentile et al (2021)^Citation21	183(50.83%)	204(48.57%)	47.29%	177(49.17%)	216(51.43%)	45.04%	360(46.15%)	420(53.85%)	780	46.15%	0.5288
Thewjitcharoen et al (2020)^Citation22	78(52.35%)	108(43.03%)	41.94%	71(47.65%)	143(56.97%)	33.18%	149(37.25%)	251(62.75%)	400	37.25%	0.0708
Gentile et al (2020)^Citation12	299(41.64%)	125(24.56%)	70.52%	419(58.36%)	384(75.44%)	52.18%	718(58.52%)	509(41.48%)	1227	58.52%	<0.0001
Lian et al (2018)^Citation23	85(50.00%)	63(48.46%)	57.43%	85(50.00%)	67(51.54%)	55.92%	170(56.67%)	130(43.33%)	300	56.67%	0.7917
Tsadik et al (2018)^Citation24	53(51.46%)	33(45.21%)	61.63%	50(48.54%)	40(54.79%)	55.56%	103(58.52%)	73(41.48%)	176	58.52%	0.4137
Hernar et al (2017)^Citation17	64(57.66%)	47(45.19%)	57.66%	47(42.34%)	57(54.81%)	45.19%	111(51.63%)	104(48.37%)	215	51.63%	0.0767
Al Hayek et al (2016)^Citation25	43(51.81%)	47(51.65%)	47.78%	40(48.19%)	44(48.35%)	47.62%	83(47.70%)	91(52.30%)	174	47.70%	0.9833
Sawatkar et. (2014)^Citation26	119(58.05%)	153(51.86%)	43.75%	86(41.95%)	142(48.14%)	37.72%	205(41.00%)	295(59.00%)	500	41.00%	0.1721
Total	1123(49.43%)	923(43.54%)	54.89%	1149(50.57%)	1197(56.46%)	48.98%	2272(51.73%)	2120(48.27%)	4392	51.73%	<0.0001

Table 3 Gender Differences in the Prevalence, Demographic and Clinical Features of LH in DM Patients (Juvenile DM)

Author (Year)	Male			Female			All				P-value
	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	Overall	LH Prevalence (%)
Singha et al (2021)^Citation27	20(43.48%)	44(67.69%)	31.25%	26(56.52%)	21(32.31%)	55.32%	46(50.55%)	45(49.45%)	91	50.55%	0.0110
McCann et al (2019)^Citation28	13(56.52%)	28(50.00%)	31.71%	10(43.48%)	28(50.00%)	26.32%	23(30.26%)	53(69.74%)	76	30.26%	0.6290
Blanco et al (2013)^Citation9	34(52.31%)	21(38.89%)	61.82%	31(47.69%)	33(61.11%)	48.44%	65(54.62%)	54(45.38%)	119	54.62%	0.1438
Conwell et al (2008)^Citation29	11(52.38%)	13(44.83%)	45.83%	10(47.62%)	16(55.17%)	38.46%	21(42.00%)	29(58.00%)	50	42.00%	0.5977
Lombardo et al (2022)^Citation37	64(66.67%)	59(50.86%)	52.03%	32(33.33%)	57(49.14%)	35.96%	96(45.28%)	116(54.72%)	212	45.28%	0.0203
Total	142(56.57%)	162(51.10%)	46.71%	109(43.43%)	155(48.90%)	41.29%	251(45.80%)	297(54.20%)	548	45.80%	0.1943

Table 4 Gender Differences in the Prevalence, Demographic and Clinical Features of LH in DM Patients (Mixed Juvenile and Adult DM)

Author (Year)	Male			Female			All				P-value
	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	Overall	LH Prevalence (%)
Yan et al (2021)^Citation30	57(55.34%)	25(64.10%)	69.51%	46(44.66%)	14(35.90%)	76.67%	103(72.54%)	39(27.46%)	142	72.54%	0.3454
Barola et al (2018)^Citation31	139(60.17%)	65(46.10%)	68.14%	92(39.83%)	76(53.90%)	54.76%	231(62.10%)	141(37.90%)	372	62.10%	0.0081
Gupta et al (2018)^Citation32	50(51.55%)	25(59.52%)	66.67%	47(48.45%)	17(40.48%)	73.44%	97(69.78%)	42(30.22%)	139	69.78%	0.3862
Blanco et al (2013)^Citation9	142(52.21%)	79(52.32%)	64.25%	130(47.79%)	72(47.68%)	64.36%	277(64.42%)	153(35.58%)	430	64.42%	0.9824
Vardar et al (2007)^Citation34	35(33.65%)	33(32.67%)	51.47%	69(66.35%)	68(67.33%)	50.36%	104(48.37%)	111(51.63%)	215	48.37%	>0.9999
Total	423(52.42%)	227(47.89%)	65.08%	384(47.58%)	247(52.11%)	60.86%	812(62.56%)	486(37.44%)	1298	62.56%	0.1187

Table 5 LH Prevalence in Patients with Different Types of Diabetes (Adult DM)

Author (year)	TIDM		T2DM		Pancreatic DM		Overall
	Present	Absent	Present	Absent	Present	Absent
Lin et al (2021)^Citation19	83 (69.17%)	37 (30.83%)					120
Arora et al (2021)^Citation20	58	55	216	140	16	15	500
Gentile et al (2021)^Citation21	118	116	326	230			780
Thewjitcharoen et al (2020)^Citation22	26	30	87	57			400
Gentile et al (2020)^Citation12			718(58.52%)	509(41.48%)			1227
Lian et al (2018)^Citation23	ND	ND					300
Tsadik et al (2018)^Citation24	103(58.52%)	73(41.48%)					176
Hernar et al (2017)^Citation17	111(51.63%)	104(48.37%)					215
Al Hayek et al (2016)^Citation25	83(47.70%)	91(52.30%)					174
Sawatkar et al (2014)^Citation26	205(41.00%)	295(59.00%)					500

Abbreviation: ND, not detected.

Table 6 LH Prevalence in Patients with T1DM

Author (Year)	Male			Female			All				P-value
	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	LH Prevalence (%)	Present No (% Among Patients with LH)	Absent No (% Among Patients Without LH)	Overall	LH Prevalence (%)
Lin et al (2021)^Citation19	48(57.83%)	22(59.46%)	68.57%	35(42.17%)	15(40.54%)	70.00%	83(69.17%)	37(30.83%)	120	69.17%	0.8673
Tsadik et al (2018)^Citation24	53(51.46%)	33(45.21%)	61.63%	50(48.54%)	40(54.79%)	55.56%	103(58.52%)	73(41.48%)	176	58.52%	0.4137
Hernar et al (2017)^Citation17	64(57.66%)	47(45.19%)	57.66%	47(42.34%)	57(54.81%)	45.19%	111(51.63%)	104(48.37%)	215	51.63%	0.0767
Al Hayek et al (2016)^Citation25	43(51.81%)	47(51.65%)	47.78%	40(48.19%)	44(48.35%)	47.62%	83(47.70%)	91(52.30%)	174	47.70%	0.9833
Sawatkar et al (2014)^Citation26	119(58.05%)	153(51.86%)	43.75%	86(41.95%)	142(48.14%)	37.72%	205(41.00%)	295(59.00%)	500	41.00%	0.1721
Total	327(55.90%)	302(50.33%)	51.99%	258(44.10%)	298(49.67%)	46.40%	103(58.53%)	73(41.49%)	1185	49.37%	0.055

Table 7 LH Prevalence in Patients of Different Age Grades

Author (Year)	Age			LH Prevalence (%)	Overall	P-value
	>18, ≤30	31–60	>60
Lin et al (2021)^Citation19	40/23 (63.49%)		43/14 (75.44%)	69.17%	120	0.1570
Arora et al (2021)^Citation20	54/58 (48.21%)	192/120 (61.54%)	44/32 (57.89%)	58.00%	500	0.0142
Gentile et al (2021)^Citation21	62.0 ± 15.0			46.15%	780
Thewjitcharoen et al (2020)^Citation22	64.8 ± 14.2			37.25%	400
Gentile et al (2020)^Citation12		396/817 (32.65%)	322/410 (43.99%)	58.52%	1227	<0.0001
Lian et al (2018)^Citation23	48.0± 3.0			56.67%	300
Tsadik et al (2018)^Citation24				58.52%	176
Hernar et al (2017)^Citation17	36.0 (18–82)			51.63%	215
Al Hayek et al (2016)^Citation25				47.70%	174
Sawatkar et al (2014)^Citation26				41.00%	239

Table 8 LH Prevalence in Patients with Different Diabetes Duration and Time of Insulin Use

Author (Year)	Duration of Diabetes			P-value	Duration of Insulin Use			P-value
	≤5	6–10	>10		≤5	6–10	>10
Lin et al (2021)^Citation19					26/28 (48.15%)	29/8 (78.38%)	28/1 (96.55%)	<0.0001
Arora et al (2021)^Citation20	83/99 (45.6%)	115/63 (64.61%)	92/48 (65.71%)	<0.0001	224/179 (55.58%)	46/21 (68.66%)	20/10 (66.67%)	<0.0001
Gentile et al (2021)^Citation21	20 ± 11				221/311 (41.54%)	58/65 (47.15%)	81/44 (64.8%)	<0.0001
Thewjitcharoen et al (2020)^Citation22	24.1 ± 8.9					13.4 ± 9.2
Gentile et al (2020)^Citation12	12 ± 9					12 ± 5
Lian et al (2018)^Citation23	10.98 ± 3.12					4.47±1.93
Tsadik et al (2018)^Citation24					65/46 (58.56%)	38/27 (58.46%)		>0.05
Hernar et al (2017)^Citation17	17.0 (1–57)
Al Hayek et al (2016)^Citation25	38/68 (35.85%)	45/23 (66.18%)		<0.0001
Sawatkar et al (2014)^Citation26	4.43 ± 4.4

Table 9 LH Prevalence in Different Body Sites

Author (Year)	Abdomen	Thighs	Arms	Other Unusual Areas	LH Prevalence(%)	Overall	P-value
Lin et al (2021)^Citation19	-	-	-	-	69.17%	120	0.1570
Arora et al (2021)^Citation20	-	-	-	-	58.00%	500	0.0142
Gentile et al (2021)^Citation21	52.4%	23.3%	19.9%	4.55%	46.15%	780
Thewjitcharoen et al (2020)^Citation22	-	-	-	-	37.25%	400
Gentile et al (2020)^Citation12	52.9%/38.3% (O/Y)	26.7%/33.4%(O/Y)	25.4%/35.8%(O/Y)	4.9%/26.2%(O/Y)	58.52%	1227	<0.0001
Lian et al (2018)^Citation23	-	-	-	-	56.67%	300
Tsadik et al (2018)^Citation24	11.4%	28.4%	15.9%	44.3%	58.52%	176
Hernar et al (2017)^Citation17	110/97 (53.14%)	82/49 (62.6%)	9/5 (64.29%)	8/13 (38.10%)	51.63%	215
Al Hayek et al (2016)^Citation25	21.6%	33.7%	27.7%	17%	47.70%	174
Sawatkar et al (2014)^Citation26	52.26%	11.91%	11.58%	23.26%	41.00%	239

Notes: Y, younger patients (31–60 years); O, older patients (>60 years).

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