Ectopic Fat and Insulin Resistance: Pathophysiology and Effect of Diet and Lifestyle Interventions

Table 1

Effect of diet and exercise on insulin sensitivity and intramyocellular lipid (IMCLs) content.

Ref.	Patients	𝑛	BMI start	Age	Intervention	Duration	Body weight loss	Effect on skeletal muscle	Effect on IMCLs
			kg/m^2	yrs			kg	insulin sensitivity
[45]	Obese NGT	12	31 ± 2	Unknown	25% caloric restriction	6 months	−8 kg	Si: no change	No change
		12	33 ± 2		12,5% caloric restriction + 12,5% exercise		−8 kg	Si 37 ± 18%, 𝑃<0.01	No change
		11	33 ± 2		15% weight loss hypocaloric diet 1200 kcal/day		−11 kg	Si 70 ± 34%, 𝑃<0.04	No change
		11	31 ± 2		controls		0 kg	Si: no change	No change
[39]	Morbid obese NGT	9	48 ± 9	39 ± 12	Diet 1200 kcal/day	6 months	−14 ± 12 kg	M value: no change	No change
		8	51 ± 8	39 ± 12	Biliopancreatic diversion		−33 ± 10 kg	M value23±3to 52 ± 11 μmol/kg FFM/min, 𝑃<0.05	1.6±1.1 to 0.2±0.4 AU, 𝑃<0.05
	Controls	7	27 ± 1	35 ± 11	Controls		Unknown	M value: no change; baseline 53 ±13 μmol/kg FFM/min	No change; baseline 0.1±0.2
[46]	Obese NGT	20	34 ± 1	42 ± 2	−700 kcal compared to normal diet	15 weeks	−11 kg	OGTT: no change	No change
					followed bij energy restriction + exercise	21 ± 2 weeks	−5 kg	OGTT: no change	No change
[41]	Obese T2DM	8	30 ± 1	47 ± 3	1200 kcal/day 3% fat diet (untill normoglycemia)	3–12 weeks (mean 7)		GDR: no change	No change
					studies after weight stabilisation period	4 weeks	−8 ± 1 kg
[42]	Obese NGT	13	33 ± 2	Unknown	−522 kcal compared to normal diet	3 months	−6 kg	M value: no change	No change
[43]	Overweight; T2DM	7	27 ± 3	55 ± 5	−25–30 kcal/kg LBM	2 weeks	BMI −1.5±0.0%	M value: no change	No change
		7	27 ± 3	46 ± 3	−25–30 kcal/kg LBM + advice to walk 2-3 td 5-6 days/week		BMI −2.3±0.1%	M value 5.3±0.3 to 8.2±0.5 mg/kg/min; 𝑃<0.001	3.8±0.4 to 3.1±0.4 IMCL/Cr, 𝑃<0.03
[44]	Morbid obese NGT	7	44 ± 6	Unknown	Diet 1200 kcal/day	6 months	−5 ± 4 kg	M value: no change	No change
[48]	Obese T2DM	13	36 ± 1	50 ± 3	VLCD 600–800 kcal/day	8 weeks	−9 ± 1 kg	HOMA-IR −0.9 is −44 ± 7%, 𝑃<0.001	No change
[49]	Obese NGT	5	36 ± 5	38 ± 12	VLCD 700 kcal/day	6 days	−2.3 kg	GDR: no change	−56%, 𝑃=0.006 (^1H-MRS)
	Obese T2DM	7	37 ± 7	43 ± 6	VLCD 700 kcal/day	6 days	−3.7 kg	GDR: no change	−40%, 𝑃=0.04 (^1H-MRS)
[50]	Obese T2DM	10	40 ± 2	55 ± 3	VLCD 500 kcal/day until 50% excess weight was lost	Mean 17 weeks	−22 kg	GDR 18.8±2.0 to 39.1±2.8 umol/kg LBM/min, 𝑃<0.001	7 ± 14 to 4 ± 1 AU, 𝑃<0.002
[51]	Obese NGT	7	33 ± 1	46 ± 2	25% caloric restriction; goal 7% weight loss	18.6±0.7 weeks	−11 ± 2%, ca −8 kg	M value increased 29 ± 7%𝑃<0.05	Decreased, 𝑃<0.05
		9	35 ± 1	42 ± 3	25% caloric restriction +3/5 days/wk exercise at 60–70% MHR	19.2±0.4 weeks	−9 ± 1%, ca −9 kg	M value increased 38 ± 9%𝑃<0.05	No change
[52]	Obese T2DM	10	34 ± 1	44 ± 3	25% caloric restriction +3/5 days/wk exercise at 60–70% MHR	16–20 weeks	−7.1±0.1% = ca 7 kg	GDR 4.1±0.6 to 6.3±0.9 mg/kg LBM/min, 𝑃<0.05	48 ± 1 to 50 ± 1 HU, 𝑃<0.01 (CT)
[53]	Obese NGT	21	33	40	−500–1000 kcal compared to normal diet with 4–6 x/wk exercise at 65–75% MHR	16 weeks	−10 kg	GDR 6.5 naar 9.7 mg/kg LBM/min 𝑃<0.05	No change
[54]	Obese IGT	11	34 ± 1	67 ± 1	−600 kcal/day compared to normal diet and aerobic exercise 5 days/wk 60 min at 75%  VO2max	12 weeks	ca −8 kg	M value 2.9±0.3 to 4.7±0.6 mg/kg LBM/min, 𝑃<0.01	3.9±0.6 to 2.5±0.3 LAI%, 𝑃<0.05
		12	35 ± 2	66 ± 1	Aerobic exercise 5 days/wk 60 min at 75%  VO2max	12 weeks	ca −3 kg	M value 3.0±0.4 to 4.2±0.7 mg/kg LBM/min, 𝑃<0.05	3.9±0.6 to 3.0±0.4 LAI%, 𝑃<0.05
[55]	Obese NGT	25	30 ± 1	66 ± 1	4-5 days/wk supervised aerobic exercise at 75% MHR	16 weeks	−1.3 kg	M value: no change	21% increase, 𝑃<0.01
[56]	Obese NGT	20	30 ± 1	59 ± 1	2x/week 30 min aerobic + 1x/week resistance exercise both at 55%  VO2max	12 weeks	no change	GDR: no change	No change
	Obese T2DM	18	30 ± 1	59 ± 1			no change	GDR 18.4±1.4 to 21.0±1.4 umol/kg/min, 𝑃<0.05	No change
[47]	Obese IFG; or IGT	8; 8	31.2±1.2; 30.0±1.0	66.9±1.7; 68.4±1.5	Diet aimed at 10% weight loss and <30% fat; Ex. 4-5 days/week 45 min/session moderate intense	16 weeks; 16 weeks	−8.5±1.5%; −1.8±0.9%	insulin-stimulated Rd + 20.6±4.8%, from ~8 mg/kg FFM/min; insulin-stimulated Rd +19.2±12.9%, from ~8 mg/kg FFM/min	Decrease 16.0±3.2%; Increase 40.8±18.2%

NGT: normal glucose tolerant; GDR: glucose disposal rate; HOMA-IR: homeostatic model assessment of insulin resistance; IGT: impaired glucose tolerant; LBM: lean body mass; T2DM: type 2 diabetes mellitus; AU: arbitrary units; LAI: mean percentage area of an individual skeletal muscle fibre that stains for lipids.