Exercise for type 2 diabetes mellitus

Diana Thomas; Elizabeth J Elliott; Geraldine A Naughton

doi:10.1002/14651858.CD002968.pub2

Ćwiczenia fizyczne u chorych na cukrzycę typu 2

Appendices

Appendix 1. Search strategy

Search terms

Unless otherwise stated, search terms are free text terms; MeSH = Medical subject heading (Medline medical index term); exp = exploded MeSH; the dollar sign ($) stands for any character(s); the question mark (?) = to substitute for one or no characters; tw = text word; pt = publication type; sh = MeSH; adj = adjacent.

Search for Diabetes mellitus, type 2

(1) exp diabetes mellitus, non‐insulin‐dependent/
(2) exp insulin resistance/
(3) impaired glucose toleranc$.tw.
(4) glucose intoleranc$.tw.
(5) insulin$ resistanc$.tw.
(6) exp obesity in diabetes/
(7) (obes$ adj diabet$).tw.
(8) (MODY or NIDDM).tw.
(9) (non insulin$ depend$ or noninsulin$ depend$ or noninsulin?depend$ or non
insulin?depend$).tw.
(10) ((typ$ 2 or typ$ II) adj diabet$).tw.
(11) ((keto?resist$ or non?keto$) adj diabet$).tw.
(12) ((adult$ or matur$ or late or slow or stabl$) adj diabet$).tw
(13) (insulin$ defic$ adj relativ$).tw.
(14) pluri?metabolic$ syndrom$.tw.
(15) 1or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14
(16) exp diabetes insipidus/
(17) diabet$ insipidus.tw.
(18) 16 or 17
(19) 15 not 18

Search for Exercise
(20) exercise.tw.
(21) physical activity.tw.
(22) exertion.tw.
(23) physical fitness.tw.
(24) walking.tw.
(25) weight lifting.tw.
(26) strength training.tw.
(27) resistance training.tw.
(28) circuit weight training.tw.
(29) exercise or exertion or physical education and training or physical fitness or sports.sh.
(30) sports.tw.
(31) 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30

Filter for randomized controlled trials*

(32) randomized‐controlled trial.pt.
(33) controlled‐clinical trial.pt.
(34) randomized‐controlled‐trials.sh.
(35) random allocation.sh.
(36) double‐blind method.sh.
(37) single‐blind method.sh.
(38) 32 or 33 or 34 or 35 or 36 or 37
(39) animal.sh.
(40) human.sh.
(41) 39 not 40
(42) 38 not 41
(43) clinical trial.pt.
(44) exp clinical trials/
(45) (clinic$ adj25 trial$).tw.
(46) ((singl$ or doubl$ or trebl$ or tripl$) adj (mask$ or blind$)).tw.
(47) Placebos.sh.
(48) placebo$.tw.
(49) random$.tw.
(50) research design.sh.
(51) (latin adj square).tw.
(52) 43 or 44 or 45 or 46 or 47 or 48 or 49 or 50 or 51
(53) 52 not 41
(54) 53 not 42

Filter for systematic reviews and meta‐analyses
(55) exp meta‐analysis/
(56) exp Review Literature/
(57) meta‐analysis.pt.
(58) review.pt.
(59) 55 or 56 or 57 or 58
(60) letter.pt.
(61) comment.pt.
(62) editorial.pt.
(63) historical‐article.pt.
(64) 60 or 61 or 62 or 63
(65) 59 not 64
(66) ((systematic$ or quantitativ$ or methodologic$) adj (review$ or overview$)).tw.
(67) meta?anal$.tw.
(68) (integrativ$ research review$ or research integration$).tw.
(69) quantitativ$ synthes$.tw.
(70) (pooling$ or pooled analys$ or mantel$ haenszel$).tw.
(71) (peto$ or der?simonian$ or fixed effect$ or random effect$).tw.
(72) 66 or 67 or 68 or 69 or 70 or 71
(73) 65 or 72
(74) limit 73 to human [Limit not valid in: Pre‐MEDLINE; records were retained]

(75) 19 and 31 and 54
(76) 19 and 31 and 74
(77) 75 or 76

Appendix 2. Risk of bias

Study	At Baseline	Randomisation	Allocation Concealed	Intention to treat	Assessor blinding	Losses accounted for
Baldi 2003	Similar	Yes	Not reported	Yes	Not reported	No losses
Cuff 2003	Similar	Yes	Not reported	Yes	Not reported	No losses
Dela 2004	Similar	Yes, by drawing lots	Not reported	Yes	Not reported	No losses
Dunstan 1998	Similar	Yes	Not reported	Not done	Not reported	Reasons given
Dunstan 2002	Similar	Yes	Not reported	Not done	Not reported	Reasons given
Loimaala 2003	Similar	Yes	Not reported	Not done	Not reported	Reason given
Maiorana 2002	Similar	Yes	Not reported	Yes	Not reported	No losses
Mourier 1997	Similar	Yes	Not reported	Not done	Not reported	No reason given
Raz 1994	Similar	Yes	Not reported	Not done	Not reported	Reasons given
Ronnemaa 1986	Similar	Yes	Not reported	Not done	Not reported	Reasons given
Tessier 2000	Similar	Yes	Not reported	Not done	Not reported	Reasons given
Tsujiuchi 2002	Similar	Yes	Not reported	Not done	Not reported	No reasons given ('variety of reasons')
Wing 1988b	Similar	Yes	Not reported	Not done	Not reported	No reasons given
Yeater	Plasma triglyceride concentrations were higher in the exercise group. No other baseline differences	Yes	Not reported	Yes	Not reported	No losses

Appendix 3. QUOROM diagramme

Papers	Excluded
Potentially relevant RCTs identified and screened for retrieval (n = 2101)
	Papers excluded (n = 2003) These papers were excluded because the abstracts revealed that the studies were not relevant to the topic of the review.
Papers retrieved for more detailed evaluation (n = 98)
	Papers excluded (n = 63) After full papers had been retrieved and assessed, those on prevention, those with co‐interventions, or in which the type 2 diabetes participants were indistinguishable from insulin impaired or normo‐glycaemic participants, were excluded. Main reasons for exclusion were: exercise was not the sole intervention, articles were reviews, studies did not compare similar groups, e.g. only one group had type 2 diabetes, all participants did not have type 2 diabetes, the intervention was less than eight weeks, the paper was on prevention rather than treatment of type 2 diabetes, the study had no control group or the study had no randomisation
Potentially appropriate RCTs to be included in the meta‐analysis (n = 35)
	RCTs excluded from meta‐analysis (n = 21) Reasons: information provided by authors resulted in exclusion for this review, e.g. data for participants with impaired glucose tolerance could not be separated from those with diabetes type 2; control group intervention included exercise also; one had 6 weeks of supervised exercise, and thereafter 'encouraged by phone'; diet co‐intervention was used, trial was not randomised, or insufficient data were provided
RCTs included in meta‐analysis (n = 14)
	RCTs withdrawn (n = 0)
RCTs with usable information (n = 14). Outcome measures included: Glycated Haemoglobin n = 13 Visceral adipose tissue n = 2 Subcutaneous adipose tissue n = 2 Body mass n = 10 Triglycerides n = 5 Maximal exercise capacity n = 3 Systolic blood pressure n = 4 Diastolic blood pressure n = 3 Fasting plasma glucose concentration n = 9 Insulin (fasting concentration) n = 7 Body Mass Index n = 7 Total cholesterol n = 5 HDL‐cholesterol n = 5 LDL‐cholesterol n = 3 Apo‐liprotein A1 n = 2 Apo‐lipoprotein B n = 2 Fat free mass n = 1 Insulin sensitivity (area under the insulinaemia curve) n = 1 Attitude to diabetes n = 1 Glycaemia (area under the curve) n = 1 Fructosamine n = 1 KITT constant (insulin tolerance test) n = 1 Fat mass n = 1

Appendix 4. Original data

Study ID / Outcome	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
01.01 Glycated haemoglobin (%)
Baldi 2003	9	8.40	1.80	9	8.40	1.80
Cuff 2003	10	6.80	1.26	9	6.87	1.20
Dela 2004	9	8.20	1.80	7	8.50	1.59
Dunstan 1998	11	8.00	1.66	10	8.30	2.21
Dunstan 2002	16	6.90	1.00	13	7.10	1.10
Loimaala 2003	24	7.60	1.40	25	8.30	1.40
Maiorana 2002	16	7.90	1.2	16	8.50	1.6
Mourier 1997	10	6.20	0.63	11	7.70	1.33
Raz 1994	19	11.70	2.60	19	12.90	4.20
Ronnemaa 1986	13	8.60	1.90	12	9.90	1.70
Tessier 2000	19	7.60	1.20	20	7.80	1.50
Tsujiuchi 2002	16	7.33	1.09	10	8.17	1.30
Tsujiuchi 2002	16	7.33	1.09	10	8.17	1.30
Wing 1988: 2nd study	13	8.20	1.08	15	9.00	1.16

01.02 Visceral adipose tissue (cm2)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Cuff 2003	10	224.80	23.40	9	258.70	36.00
Mourier 1997	10	80.40	22.14	11	134.90	33.83

01.03 Subcutaneous adipose tissue (cm2)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Cuff 2003	10	446.90	48.70	9	566.70	27.00
Mourier 1997	10	186.70	44.59	11	260.30	71.64

01.04 Body Mass (kg)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Baldi 2003	9	114.00	12.30	9	110.90	22.20
Cuff 2003	10	86.60	12.33	9	97.60	19.50
Dela 2004	9	97.00	12.00	7	92.00	18.52
Dunstan 1998	11	83.20	12.30	10	83.70	12.00
Dunstan 2002	16	86.20	10.90	13	86.40	12.10
Maiorana 2002	16	88.70	17.60	16	88.70	17.60
Mourier 1997	10	83.80	12.33	11	84.20	15.26
Ronnemaa 1986	13	83.20	19.50	12	83.30	12.40
Tessier 2000	19	83.00	17.60	20	79.50	14.60
Wing 1988: 2nd study	13	94.80	21.30	15	96.40	19.74

01.05 Triglycerides (mmol/litre)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Maiorana 2002	16	2.20	1.20	16	2.70	1.60
Mourier 1997	8	1.79	1.08	8	2.33	0.63
Raz 1994	19	1.90	0.70	19	2.20	0.06
Ronnemaa 1986	13	1.91	0.97	12	1.75	0.62
Wing 1988: 2nd study	13	1.42	0.69	15	1.64	0.74

01.06 Maximal exercise capacity (VO2max)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Loimaala 2003	24	33.80	5.50	25	31.80	6.60
Mourier 1997	10	32.40	4.11	11	23.00	4.97
Ronnemaa 1986	13	29.30	6.20	12	25.90	6.70

01.07 Systolic blood pressure (mmHg)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Dunstan 1998	11	127.00	9.96	10	127.00	12.64
Dunstan 2002	16	138.30	17.80	13	144.50	15.50
Loimaala 2003	24	138.00	16.00	25	144.00	14.00
Wing 1988: 2nd study	13	130.00	18.05	15	135.00	23.22

01.08 Diastolic blood pressure (mmHg)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Dunstan 1998	11	73.00	6.64	10	72.00	6.32
Dunstan 2002	16	73.60	8.80	13	74.10	6.40
Wing 1988: 2nd study	13	83.00	7.22	15	85.00	15.48

01.09 Fasting plasma glucose concentration (mmol/litre)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Baldi 2003	9	11.40	2.40	9	11.00	3.00
Dela 2004	9	10.90	3.60	7	12.10	3.44
Dunstan 1998	11	9.40	2.66	10	9.80	4.11
Maiorana 2002	16	9.80	2.00	16	12.00	2.00
Mourier 1997	10	9.50	1.58	11	8.60	1.66
Raz 1994	19	10.20	3.30	19	12.30	4.40
Ronnemaa 1986	13	10.50	4.40	12	11.20	2.20
Tessier 2000	19	9.20	2.50	20	8.40	2.30
Wing 1988: 2nd study	13	8.40	1.81	15	9.20	2.71

01.10 Insulin (fasting concentration) (pmol/litre)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Baldi 2003	9	21.10	12.30	9	30.90	22.50
Dela 2004	9	134.00	81.00	7	131.00	68.79
Dunstan 1998	11	63.10	41.83	10	93.80	39.82
Mourier 1997	10	21.10	7.90	11	21.90	12.60
Ronnemaa 1986	13	15.40	10.80	12	15.50	8.20
Tessier 2000	19	17.10	8.70	20	17.00	6.90
Wing 1988: 2nd study	13	18.30	11.19	15	17.60	16.25

01.11 Body Mass Index (kg/m2)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Dela 2004	9	31.00	3.00	7	30.00	5.29
Dunstan 1998	11	28.10	2.65	10	30.40	3.48
Loimaala 2003	24	28.90	3.80	25	29.80	3.70
Maiorana 2002	16	29.60	13.20	16	29.60	13.60
Mourier 1997	10	30.60	1.90	11	30.00	5.31
Raz 1994	19	31.50	4.30	19	30.60	4.20
Tessier 2000	19	30.60	5.40	20	29.40	3.80

Appendix 5. Original data (continued)

Study ID / Outcome	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
01.12 Total cholesterol (mmol/litre)
Maiorana 2002	16	4.60	0.80	16	4.60	0.80
Mourier 1997	8	5.34	1.42	8	5.40	1.16
Raz 1994	19	5.60	1.00	19	6.00	1.00
Ronnemaa 1986	13	6.37	0.90	12	6.10	1.00
Wing 1988: 2nd study	13	4.21	0.83	15	4.44	0.62

01.13 HDL‐cholesterol (mmol/litre)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Maiorana 2002	16	1.10	0.40	16	1.00	0.40
Mourier 1997	8	1.02	0.17	8	1.12	0.18
Raz 1994	19	1.10	0.30	19	1.10	0.30
Ronnemaa 1986	13	1.29	0.36	12	1.26	0.31
Wing 1988: 2nd study	13	0.94	0.18	15	0.96	0.19

01.14 LDL‐cholesterol (mmol/litre)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Maiorana 2002	16	2.50	0.80	16	2.40	0.80
Mourier 1997	8	4.34	1.39	8	4.29	1.16
Ronnemaa 1986	13	4.29	0.87	12	4.11	0.90

01.17 RFI (risk factor index = total cholesterol/HDL)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Mourier 1997	8	5.24	1.59	8	4.82	1.34
Raz 1994	19	5.09	1.30	19	5.45	1.30
Ronnemaa 1986	13	4.94	1.26	12	4.80	1.31
Wing 1988: 2nd study	13	4.48	1.01	15	4.65	0.81

01.18 Fat free mass (kg)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Baldi 2003	9	76.90	3.30	9	70.60	9.00

01.19 Insulin sensitivity (AUC insulinaemia)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Tessier 2000	19	400.00	212.00	20	269.00	131.00

01.24 Fat mass (kg)
Study ID	Exercise N	Exercise Mean	Exercise SD	Control N	Control Mean	Control SD
Baldi 2003	9	37.00	10.50	9	40.30	18.90

Analysis 1.1

Comparison 1 Exercise vs no exercise, Outcome 1 Glycated haemoglobin (%).

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Analysis 1.2

Comparison 1 Exercise vs no exercise, Outcome 2 Visceral adipose tissue (cm2).

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Analysis 1.3

Comparison 1 Exercise vs no exercise, Outcome 3 Subcutaneous adipose tissue (cm2).

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Analysis 1.4

Comparison 1 Exercise vs no exercise, Outcome 4 Body Mass (kg).

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Analysis 1.5

Comparison 1 Exercise vs no exercise, Outcome 5 Triglycerides (mmol/litre).

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Analysis 1.6

Comparison 1 Exercise vs no exercise, Outcome 6 Maximal exercise capacity (VO2max)(ml/(kg*min)).

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Analysis 1.7

Comparison 1 Exercise vs no exercise, Outcome 7 Systolic blood pressure (mmHg).

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Analysis 1.8

Comparison 1 Exercise vs no exercise, Outcome 8 Diastolic blood pressure (mmHg).

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Analysis 1.9

Comparison 1 Exercise vs no exercise, Outcome 9 Fasting plasma glucose concentration (mmol/L).

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Analysis 1.10

Comparison 1 Exercise vs no exercise, Outcome 10 Insulin (fasting concentration (pmol/litre).

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Analysis 1.11

Comparison 1 Exercise vs no exercise, Outcome 11 Body Mass index (kg/m2).

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Analysis 1.12

Comparison 1 Exercise vs no exercise, Outcome 12 Total cholesterol (mmol/l).

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Analysis 1.13

Comparison 1 Exercise vs no exercise, Outcome 13 HDL‐cholesterol (mmol/).

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Analysis 1.14

Comparison 1 Exercise vs no exercise, Outcome 14 LDL‐cholesterol (mmol/).

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Comparison 1. Exercise vs no exercise

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Glycated haemoglobin (%) Show forest plot	13	361	Mean Difference (IV, Fixed, 95% CI)	‐0.62 [‐0.91, ‐0.33]

2 Visceral adipose tissue (cm2) Show forest plot	2	40	Mean Difference (IV, Fixed, 95% CI)	‐45.54 [‐63.76, ‐27.31]

3 Subcutaneous adipose tissue (cm2) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

4 Body Mass (kg) Show forest plot	10	248	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐3.83, 3.76]

5 Triglycerides (mmol/litre) Show forest plot	5	139	Mean Difference (IV, Fixed, 95% CI)	‐0.25 [‐0.48, ‐0.02]

6 Maximal exercise capacity (VO2max)(ml/(kgmin)) Show forest plot*	3	95	Mean Difference (IV, Fixed, 95% CI)	4.84 [2.55, 7.12]

7 Systolic blood pressure (mmHg) Show forest plot	4	127	Mean Difference (IV, Fixed, 95% CI)	‐4.16 [‐9.46, 1.14]

8 Diastolic blood pressure (mmHg) Show forest plot	3	78	Mean Difference (IV, Fixed, 95% CI)	‐0.13 [‐3.70, 3.45]

9 Fasting plasma glucose concentration (mmol/L) Show forest plot	9	238	Mean Difference (IV, Fixed, 95% CI)	‐0.45 [‐1.09, 0.18]

10 Insulin (fasting concentration (pmol/litre) Show forest plot	7	168	Mean Difference (IV, Fixed, 95% CI)	‐0.71 [‐4.13, 2.71]

11 Body Mass index (kg/m2) Show forest plot	7	216	Mean Difference (IV, Fixed, 95% CI)	‐0.21 [‐1.35, 0.93]

12 Total cholesterol (mmol/l) Show forest plot	5	139	Mean Difference (IV, Fixed, 95% CI)	‐0.11 [‐0.41, 0.18]

13 HDL‐cholesterol (mmol/) Show forest plot	5	139	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐0.10, 0.06]

14 LDL‐cholesterol (mmol/) Show forest plot	3	73	Mean Difference (IV, Fixed, 95% CI)	0.12 [‐0.29, 0.53]

Comparison 1. Exercise vs no exercise

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Ćwiczenia fizyczne u chorych na cukrzycę typu 2

Appendices

Appendix 1. Search strategy

Appendix 2. Risk of bias

Appendix 3. QUOROM diagramme

Appendix 4. Original data

Appendix 5. Original data (continued)

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Appendices

Appendix 1. Search strategy

Appendix 2. Risk of bias

Appendix 3. QUOROM diagramme

Appendix 4. Original data

Appendix 5. Original data (continued)

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