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Gaffney, CJ

Greenhaff, PL

Mansell, P

Stephens, FB

Tsintzas, K

Diabetologia

Open Research Exeter

Dietary	fat	oxidation	is	elevated	in	middle-aged	type	2	diabetes			Gaffney,	C.	J1.	Mansell,	P.,2	Greenhaff,	P.	L.2,	Tsintzas,	K.2,	&	Stephens,	F.	B.1		1	Sport	&	Health	Sciences,	University	of	Exeter,	UK	2	MRC/ARUK	Centre	for	Musculoskeletal	Ageing	Research,	University	of	Nottingham,	UK		Background	and	Aims:	Older	individuals	have	increased	delivery	of	endogenous	fat	to	skeletal	muscle,	which	may	predispose	to	insulin	resistance	if	fat	oxidation	is	reduced.	Likewise,	insulin	resistance	increases	the	delivery	and	storage	of	dietary	and	endogenous	fat	in	skeletal	muscle.	The	aim	of	the	present	study	was	to	investigate	the	effect	of	type	2	diabetes	(T2D)	and	age	on	dietary	fat	oxidation.			Materials	and	Methods:	Seven	middle	age	(46.0	±	1.1	y)	and	seven	older	(63.4	±	0.6	y)	patients	with	T2D	(metformin	and/or	diet	control	for	4.8	±	1.1	y)	were	matched	with	seven	middle	age	(46.1	±	2.9	y)	normoglycaemic	controls	for	BMI	(31.1	±	1.5;	29.6	±	1.1;	29.6	±	1.3	kg/m2,	respectively),	%	body	fat	by	DXA	(28.5	±	2.3;	28.2	±	4.0;	±	30.6	±	1.2	%,	respectively),	and	habitual	physical	activity	(measured	and	self-reported).	Subjects	were	prescribed	a	eucaloric	diet	(Henry	equation)	for	72	h	preceding	a	fasted	oral	glucose	tolerance	test	(OGTT).	During	this	time,	interstitial	glucose	was	continuously	measured	using	a	subcutaneous	probe.	Twenty-four	h	before	the	OGTT,	subjects	consumed	a	meal	replacement	drink	(330	kcal:	44g	carbohydrate,	11g	fat,	and	14g	protein)	containing	15	mg/kg	[2H31]palmitate	and	0.2	g/kg	[18O]water	and	were	asked	to	collect	all	passed	urine	for	the	following	10	h.	Indirect	calorimetry	was	performed	to	determine	respiratory	exchange	ratio	(RER)	before	and	at	the	end	of	the	120	min	OGTT.	Blood	samples	were	taken	every	15	min	throughout	the	OGTT	for	measurement	of	blood	glucose,	serum	insulin	and	free	fatty	acid	(FFA)	concentration.	Urine	samples	were	analysed	for	2H/1H	and	18O/16O	isotope	ratios	by	infrared	spectroscopy	in	order	to	determine	dietary	fat	oxidation	and	total	body	water,	respectively.	Two-way	and	one-way	ANOVA	was	used	to	detect	any	differences	in	the	blood	and	urine	measurements,	respectively.	Data	are	presented	as	mean	±	SEM.			Results:		Average	blood	glucose	during	the	OGTT	was	greater	(P<0.001)	in	T2D	(11.9	±	0.9	and	10.7	±	0.8	mmol/L	for	middle	age	and	older,	respectively)	than	control	(7.6	±	0.5	mmol/L),	and	average	serum	insulin	was	almost	half	(50.3	±	5.05	mIU/L	and	56.0	±	7.15	mIU/L	vs.	93.9	±	11.5	mIU/L,	respectively;	P=0.09).	Average	24	h	interstitial	glucose	was	also	higher	in	T2D	(9.9	±	0.18	and	7.6	±	0.14	mmol/L	for	middle	age	and	older,	respectively)	compared	to	control	(6.4	±	0.07;	P<0.001).	There	was	a	trend	(P=0.08)	for	10	h	dietary	fat	oxidation	to	be	greater	in	middle	age	T2D	(22.6	±	1.6	%	recovery	of	dose)	than	older	T2D	(13.9	±	3.3	%)	and	control	(13.4	±	2.7	%).	Furthermore,	fasting	plasma	FFA	in	middle	age	T2D	(0.39	±	0.05	mmol/L)	was	lower	(P=0.05)	than	older	T2D	(0.48	±	0.05	mmol/L)	and	control	(0.49	±	0.05	mmol/L),	but	higher	(P<0.05)	at	the	end	of	the	OGTT	(0.10	±	0.03	vs.	0.05	±	0.01	and	0.04	±	0.01	mmol/L,	respectively).	RER	increased	during	the	OGTT	in	all	groups	(P<0.001)	from	similar	fasted	values	(0.74	±	0.05,	0.75	±	0.04,	and	0.74	±	0.03	for	controls,	middle	age	T2D,	and	older	T2D,	respectively)	to	similar	fed	values	(0.82	±	0.03,	0.83	±	0.02,	and	0.84	±	0.03,	respectively).		Conclusion:	Despite	similar	fasting	fat	oxidation,	dietary	fat	oxidation	was	increased	in	middle	age	T2D	compared	to	age	matched	controls.	Combined	with	an	inability	to	suppress	plasma	FFA	with	feeding,	this	suggests	excessive	postprandial	fat	delivery	to	skeletal	muscle	in	T2D.	The	lower	dietary	fat	oxidation	in	older	T2D	does	not	appear	to	exacerbate	insulin	resistance.				2891	

Dietary fat oxidation is elevated in middle-aged type 2 diabetes

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