The effects of different doses of exercise on pancreatic β-cell function in patients with newly diagnosed type 2 diabetes: study protocol for and rationale behind the “DOSE-EX” multi-arm parallel-group randomised clinical trial

Table 4 Outcome assessment during the intervention (SPIRIT figure)

Participant timeline	Week	− 8 >	− 2	− 1	0	4	12	17	18	18
	Domain	Visit 0	Visit 1	Visit 2	Visit 3	Visit 4	Visit 5	Visit 6	Visit 7	Visit 8
Intervention period					X	X	X
Primary outcome
Hyperglycaemic clamp	β-cell function			X					X
Secondary and exploratory outcomes
Clinical blood sampling	Clinical, functional, metabolic markers of mechanisms¹	X	X			X	X	X
Urine sampling	Systemic markers of oxidative stress²		X			X	X	X
Mixed meal tolerance test	Glycaemic control during mixed meal tolerance test³		X					X
Continuous glucose monitoring	24-h glucose profile		X					X
Muscle and fat biopsies	Muscle and fat profiling⁴			X					X
Cardiovascular procedures
Home blood pressure	Resting systolic and diastolic blood pressure		X			X	X	X
Body composition
Magnetic resonance imaging	Visceral fat mass				X					X
Magnetic resonance spectroscopy	Pancreatic and hepatic fat deposition				X					X
Dual-energy X-ray absorptiometry	BW, BMI, LBM, FM		X					X
Physical function
Cardiorespiratory fitness	Maximal aerobic capacity		X					X
Muscular strength	1RM		X					X
Physical activity behaviour	Accelerometer-based physical activity monitors		X			X	X	X
Patient-reported outcomes
Mental and physical well-being	SF36 questionnaire			X					X
Quality of life	SF36 questionnaire			X					X
Satiety	VAS		X					X
Dietary records	3-day record			X		X	X	X

BW, body weight; BMI, body mass index; LBM, lean body mass; FM, fat mass; 1RM, one-repetition maximum; VAS, visual analogue scale
1. Total cholesterol, low- and high-density lipoprotein, HbA1c, interferon-ɣ, interleukin 10, interleukin 8, interleukin 6, interleukin 1, tumour necrosis factor α, Advanced Glycation End-products (AGE), receptor for AGE (RAGE).
2. 8-oxoGuo and 8-oxodG
3. iAUC, tAUC of glucose, insulin, glucagon and C-peptide, circulation markers of appetite regulation and gastric emptying.
4. Muscle progenitor cell isolation, snap freeze and tissue-tek.

ISSN: 1745-6215