Is Helicobacter pylori infection associated with glycemic control in diabetics?

Table 1 Characteristics of the selected studies in our systematic review

Ref.	Location	Study design and type of intervention	DM patients,n (HP+/HP-)1	Diagnosis ofH. pylori	Parameter(s) measured	Glycemic control(HP+ vs HP-)	Quality score2
de Luis et al[43], 2000	Spain	Observational;	13 (13/13)	UBT and serologic test	HbA1c	ND	9
		before and after eradication (6-mo-follow-up)
Arslan et al[28], 2000	Turkey	Observational;	88 (49/39)	Serologic test	HbA1c	ND	8
		HP+ vs HP-
Ko et al[29], 2001	Hong Kong, China	Observational;	63 (32/31)	RUT	HbA1c and FPG	ND	9
		HP+ vs HP-
Jones et al[30], 2002	Australia	Observational;	63 (15/48)	Serologic test	HbA1c	ND	9
		HP+ vs HP-
Ojetti et al[18], 2002	Italy	Observational;	34 (13/21)	UBT and histology	HbA1c	Worse	7
		reinfected vs not reinfected (1-yr-follow-up)
Candelli et al[31], 2003	Italy	Observational;	121 (34/87)	UBT and serologic test	HbA1c	ND	8
		HP+ vs HP-
Wang et al[32], 2003	China	Observational;	94 (75/19)	Serologic test	HbA1c and FPG	ND	8
		HP+ vs HP-
Candelli et al[33], 2004	Italy	Observational;	58 (29/29)	UBT	HbA1c	ND	8
		HP+ vs HP-
		before and after eradication (6-mo-follow-up)
Agrawal et al[38], 2005	India	Observational;	80 (50/30)	RUT	FPG	Worse	8
		HP+ vs HP-
Moghimi et al[41], 2007	Iran	RCT	41 (22/19)	UBT	HbA1c decrease and FPG decrease	ND	3 (Jadad score)
		eradication vs non-eradication (3-mo-follow-up)
Ojetti et al[19], 2007	Italy	Observational;	40 (11/29)	UBT and histology	HbA1c	Worse	7
		reinfected vs not reinfected (5-yr-follow-up)
Toporowska-Kowalska et al[34], 2007	Poland	Observational;	198 (48/150)	UBT	HbA1c	Worse	7
		HP+ vs HP-
Khalil et al[44], 2007	Belgium	Observational;	100 (49/51)	UBT	HbA1C	ND	7
		before and after eradication (12-mo-follow-up)
Demir et al[35], 2008	Turkey	Observational;	141 (87/54)	RUT and histology	HbA1c and FPG	ND	9
		HP+ vs HP-
Lu et al[40], 2010	China	Observational;	80 (49/31)	UBT and histology	Insulin and C-peptide	Worse	8
		HP+ vs HP-
Candelli et al[17], 2012	Italy	Observational;	69 (17/52)	UBT	HbA1c	ND	8
		HP+ vs HP-
Wei[39], 2012	China	Observational;	68 (38/30)	RUT	FPG	Worse	7
		HP+ vs HP-
Zhou et al[36], 2012	China	Observational;	180 (84/96)	Serologic test	HbA1c, insulin and C-peptide	ND	8
		HP+ vs HP-
Vafaeimanesh et al[42], 2013	Iran	RCT;	93 (46/47)	UBT	HbA1c decrease and FPG decrease	ND	3 (Jadad score)
		eradication vs noneradication (6-mo-follow-up)
Peng et al[37], 2013	China	Observational;	85 (43/42)	RUT and histology	HbA1c and FPG	Worse	7
		HP+ vs HP-
Wada et al[45], 2013	Japan	Observational;	72 (72/72)	UBT and histology	HbA1c	ND	7
		before and after eradication (6-mo-follow-up)

¹HP+ includes those who did not receive/failed eradication treatment, and those who were reinfected; HP- includes those who received successful eradication treatment;

²Quality score is presented in each study by reference to Quality Assessment Forms, except for the two RCTs assessed using the Jadad Scale. DM: Diabetes mellitus; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin; HP+: Helicobacter pylori-positive; HP-: H. pylori-negative; ND: No difference; RCT: Randomized controlled trial; RUT: Rapid urease test; UBT: ¹³C-urea breath test.

Table 2 Population information of the selected studies

Ref.	DM type	Age (yr)	Sex (M/F, n)	DM duration (yr)	Type of therapy for DM	GI symptoms, n
de Luis et al[43], 2000	T1DM	44.9 ± 15.5	4/9	13.49 ± 7.0	Insulin	10 with dyspepsia
				(1-33)
Arslan et al[28], 2000	T1DM	12.6 ± 4.2	36/52	HP+: 3.85 ± 3.62;	Insulin	5 had upper GI symptoms
				HP-: 2.30 ± 2.12 (P = 0.02)1
				(0-13)
Ko et al[29], 2001	T2DM	49.9 ± 12.0	29/34	HP+: 5.2 ± 5.7;	Irrespective	29 had upper GI symptoms
				HP-: 7.3 ± 6.6 (NS)
				(1-26; median: 3)
Jones et al[30], 2002	T1DM and T2DM	44.7 ± 2.99	25/38	16.6 ± 1.4	Insulin; oral drugs	GI symptoms occurred frequently
Ojetti et al[18], 2002	T1DM	42 ± 9	18/16	NA	Insulin	None had GI symptoms
Candelli et al[31], 2003	T1DM	15 ± 6	65/56	6.6 ± 4.6	Insulin	A proportion had GI symptoms
Wang et al[32], 2003	T2DM	(28-83)	44/50	HP+: 5.8 ± 2.2;	Insulin and oral drugs	A proportion had GI symptoms2
				HP-: 9.3 ± 6.5 (P < 0.05)1
Candelli et al[33], 2004	T1DM	13.35 ± 3.62	28/30	NA	Insulin	35 had GI symptoms
Agrawal et al[38], 2005	T2DM	52.8 ± 11.1	62/18	NA	NA	36 had GI symptoms
Moghimi et al[41], 2007	T2DM	NA	NA	No difference in two groups	Insulin and oral drugs	NA
Ojetti et al[19], 2007	T1DM	48 ± 9	23/17	27.5 ± 12.5	Insulin	NA
Toporowska-Kowalska et al[34], 2007	T1DM	14.38 ± 3.75	NA	(0.5-16)	Insulin	NA
Khalil et al[44], 2007	T1DM	14.2 ± 2.8	56/44	6.2 ± 2.3	Insulin	45 had vague abdominal pain
Demir et al[35], 2008	T2DM	52.0 ± 8.2	44/97	6.1 ± 5.9	Insulin, oral drugs or diet alone	All had GI symptoms
				HP+: 5.9 ± 6.1;
				HP-: 6.28 ± 5.9 (NS)
Lu et al[40], 2010	T1DM	18.6 ± 10.6	45/35	No difference in two groups	Insulin	NA
Candelli et al[17], 2012	T1DM	16.8 ± NA (9-21)	41/28	NA	Insulin	A proportion had GI symptoms
Wei[39], 2012	T2DM	50.0 ± 11.2	36/32	NA	NA	NA
Zhou et al[36], 2012	T2DM	59.22 ± 2.57	87/93	NA	NA	NA
Vafaeimanesh et al[42], 2013	T2DM	55.3 ± 10.4	50/43	NA	Non-insulin users	A proportion had GI symptoms
Peng et al[37], 2013	T2DM	50.1 ± 10.3	51/34	No difference in two groups	NA	NA
Wada et al[45], 2013	T2DM	63.7 ± 1.1	55/17	NA	NA	NA

¹Significant difference in the duration of diabetes for the HP+ vs HP-;

²Prevalence of GI symptoms was higher in the HP+ group than in the HP- group. Data are presented as mean ± SD (range). DM: Diabetes mellitus; HP+: Helicobacter pylori–positive; HP-: H. pylori–negative; GI: Gastrointestinal; NA: Not available; NS: Not significant; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus.

Table 3 Glycosylated hemoglobin levels in Helicobacter pylori-positive diabetics before and after eradication treatment

Ref.	Eradication regimen	Before treatment	After treatment			P value
			3 mo	6 mo	12 mo
de Luis et al[43], 2000	A: 2000 mg, C: 1000 mg, O: 40 mg; 10 d	7.7 ± 1.4	NA	7.3 ± 1.0	NA	> 0.05
Candelli et al[33], 2004	< 14 yr: A: 50 mg/kg, C: 30 mg/kg, R: 2 mg/kg; 7 d	8.2 ± 1.0	NA	8.3 ± 1.0	NA	> 0.05
	> 14 yr: A: 2000 mg, C: 750 mg, R: 20 mg; 7 d
Khalil et al[44], 2007	Two antibiotics among A, C or M; O; 7 d	7.4 ± 1.3	NA	NA	7.9 ± 1.1	> 0.05
Wada et al[45], 2013	A: 1500 mg, C: 800 mg, L: 60 mg or O: 40 mg or R: 40 mg; 7 d	6.9 ± 0.1	7.0 ± 0.1	7.0 ± 0.1	NA	> 0.05

Data are presented as mean ± SE. A: Amoxicillin; C: Clarithromycin; L: Lansoprazole; M: Metronidazole; NA: Not available; O: Omeprazole; R: Rabeprazole.