Type 2 Diabetes–Prevention Diet and All-Cause and Cause-Specific Mortality

A Prospective Study

Chun-Rui Wang; Tian-Yang Hu; Fa-Bao Hao; Nan Chen; Yang Peng; Jing-Jing Wu; Peng-Fei Yang; Guo-Chao Zhong

Am J Epidemiol. 2022;191(3):472-486.

Abstract and Introduction

Abstract

We aimed to examine whether type 2 diabetes–prevention diet, a dietary pattern previously developed for reducing type 2 diabetes risk, was associated with mortality in a US population. A population-based cohort of 86,633 subjects was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993–2015). Dietary information was collected with a food frequency questionnaire. A dietary diabetes risk-reduction score was calculated to reflect adherence to this dietary pattern, with higher scores representing better adherence. Hazard ratios (HRs) and absolute risk differences (ARDs) in mortality rates per 10,000 person-years were calculated. After a mean follow-up of 13.6 years, 17,532 all-cause deaths were observed. Participants with the highest versus the lowest quintiles of dietary diabetes risk-reduction score were observed to have decreased risks of death from all causes (HR = 0.76, 95% CI: 0.72, 0.80; ARD: −81.94, 95% CI: −93.76, −71.12), cardiovascular disease (HR = 0.73, 95% CI: 0.66, 0.81; ARD: −17.82, 95% CI: −24.81, −11.30), and cancer (HR = 0.85, 95% CI: 0.78, 0.94; ARD: −9.92, 95% CI: −15.86, −3.59), which were modified by sex, smoking status, or alcohol consumption in subgroup analyses (P for interaction < 0.05 for all). In conclusion, a type 2 diabetes–prevention diet confers reduced risks of death from all causes, cardiovascular disease, and cancer in this US population.

Introduction

Type 2 diabetes is a major public health concern worldwide and is a well-established predisposing factor for cardiovascular disease^[1] and cancer,^[2] which represent 2 leading global causes of death. Dietary behaviors play a critical role in public health; unhealthy diet is ranked as the most common cause of death in the US population.^[3] Hence, it is essential to investigate the potential associations of dietary behaviors with health outcomes.

A type 2 diabetes–prevention diet was proposed by Rhee et al. in 2015^[4] and features high intakes of cereal fiber, polyunsaturated fatty acids, coffee, and nuts and low intakes of carbohydrates, trans-fatty acids, red and processed meat, and sugar-sweetened beverages.^[4] Compared with other established dietary patterns (e.g., the Mediterranean diet), the type 2 diabetes–prevention diet captures key dietary elements closely related to the risk of type 2 diabetes and is developed primarily for facilitating the prevention of this disease,^[4] resulting in inclusion of some components that are not part of other established dietary patterns (e.g., coffee and glycemic index); moreover, adherence to the type 2 diabetes–prevention diet could improve insulin sensitivity and reduce inflammation levels.^[4–6] Recently, the type 2 diabetes–prevention diet was found to be associated with reduced risks of hepatocellular carcinoma,^[7] breast cancer,^[8] and pancreatic cancer.^[9] However, whether the type 2 diabetes–prevention diet is associated with mortality remains unknown. Some studies have investigated the associations between individual components of the type 2 diabetes–prevention diet with the risk of mortality,^[10–16] but they fail to consider the potential interactions among dietary components. Therefore, assessment of dietary patterns, which include multiple foods or nutrients simultaneously and thus can capture the potential interactions among them, may provide a more accurate estimate for diet-disease associations.

Hence, in this study, we aimed to examine the hypothesis that adherence to the type 2 diabetes–prevention diet is associated with all-cause and cause-specific mortality in the US population.

1 2 3 4

Next Section

Abstract and Introduction
Methods
Results
Discussion
References

Table 1. Baseline Characteristics of Study Population According to Quintiles of Dietary Diabetes Risk-Reduction Score, a Post Hoc Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, United States, 1993–2015
Characteristic	Quintiles of Dietary Diabetes Risk Reduction Score, Range (Median)
	9–19 (17) (n = 16,302)			20–22 (21) (n = 17,623)			23–24 (23) (n = 13,339)			25–27 (26) (n = 18,023)			28–40 (30) (n = 21,346)
	Mean (SD)	No.	%	Mean (SD)	No.	%	Mean (SD)	No.	%	Mean (SD)	No.	%	Mean (SD)	No.	%
Age, years	64.5 (5.6)			65.1 (5.7)			65.3 (5.7)			65.5 (5.7)			65.6 (5.7)
Male sex		9,745	59.8		8,962	50.9		6,176	46.3		7,330	40.7		7,463	35.0
Ethnicity
Non-Hispanic White		14,982	91.9		16,316	92.6		12,263	91.9		16,470	91.4		19,241	90.1
Non-Hispanic Black		785	4.8		552	3.1		341	2.6		416	2.3		454	2.1
Hispanic		239	1.5		237	1.3		172	1.3		246	1.4		310	1.5
Others^a		296	1.8		518	2.9		563	4.2		891	4.9		1,341	6.3
Married or living as married		13,082	80.2		14,052	79.7		10,611	79.5		14,191	78.7		16,197	75.9
Body mass index^b	28.0 (4.9)			27.5 (4.8)			27.1 (4.6)			26.7 (4.5)			25.8 (4.3)
Educational level
Some college or below		11,753	72.1		11,762	66.7		8,490	63.6		10,870	60.3		11,604	54.4
College graduate		2,377	14.6		2,969	16.8		2,448	18.4		3,411	18.9		4,362	20.4
Postgraduate		2,172	13.3		2,892	16.4		2,401	18.0		3,742	20.8		5,380	25.2
Alcohol consumption, g/day	7.6 (20.4)			8.7 (21.6)			9.7 (24.3)			10.7 (26.9)			11.6 (30.1)
Smoking status
Current		2,114	13.0		1914	10.9		1,248	9.4		1,451	8.1		1,272	6.0
Past		6,316	38.7		7,040	39.9		5,556	41.7		7,573	42.0		9,448	44.3
Never		7,872	48.3		8,669	49.2		6,535	49.0		8,999	49.9		10,626	49.8
Physical activity, minutes/week^c	107.0 (117.2)			114.1 (120.0)			120.5 (119.7)			126.9 (121.9)			145.8 (129.4)
Energy intake from diet, kcal/day	1937.8 (767.6)			1790.4 (769.0)			1697.6 (739.5)			1646.8 (711.3)			1639.6 (653.4)
HEI-2015 score	56.5 (7.9)			62.7 (7.5)			66.3 (7.2)			69.5 (7.0)			75.1 (6.8)
Plant-based diet index score	52.5 (5.9)			53.4 (6.3)			53.5 (6.4)			53.9 (6.5)			55.0 (6.5)
History of hypertension		5,161	31.7		5,435	30.8		3,927	29.4		5,110	28.4		5,449	25.5
Family history of cancer		9,082	55.7		9,906	56.2		7,465	56.0		10,310	57.2		12,088	56.6
Aspirin use
Yes		6,909	42.4		7,682	43.6		5,771	43.3		7,952	44.1		9,328	43.7
No		9,393	57.6		9,941	56.4		7,568	56.7		10,071	55.9		12,018	56.3
Single or multivitamin supplement use
Yes		11,031	67.7		13,183	74.8		10,414	78.1		14,612	81.1		18,506	86.7
No		5,271	32.3		4,440	25.2		2,925	21.9		3,411	18.9		2,840	13.3
Energy-adjusted food and nutrient intakes
Glycemic index	56.6 (3.6)			54.8 (3.8)			53.7 (3.8)			52.6 (3.8)			50.7 (3.7)
Cereal fiber, g/day	9.1 (4.8)			10.4 (5.5)			11.2 (5.9)			12.1 (6.2)			15.1 (7.2)
Ratio of polyunsaturated to saturated fatty acids	0.6 (0.5)			0.7 (0.2)			0.7 (0.3)			0.8 (0.5)			1.0 (0.4)
Trans-fatty acids, g/day	6.0 (3.4)			4.9 (3.2)			4.1 (2.8)			3.3 (2.5)			2.1 (1.9)
Sugar-sweetened beverages, g/day	537.9 (705.7)			283.7 (436.3)			194.3 (349.0)			138.5 (263.2)			78.4 (186.6)
Nuts, g/day	1.9 (4.8)			3.8 (8.3)			5.0 (10.4)			7.1 (13.8)			13.9 (24.6)
Coffee, g/day	654.1 (769.9)			827.5 (806.9)			875.6 (800.0)			907.6 (788.9)			950.2 (778.4)
Red and processed meat, g/day	22.0 (20.8)			15.4 (17.3)			11.7 (13.9)			8.9 (11.4)			4.8 (7.9)
Polyunsaturated fatty acids, g/day	14.8 (7.7)			14.4 (8.3)			13.7 (8.2)			13.5 (8.2)			14.0 (8.4)
Saturated fatty acids, g/day	26.8 (13.8)			22.7 (13.1)			19.8 (11.6)			17.6 (10.5)			14.5 (8.4)
Fruit, g/day	199.2 (172.0)			236.1 (185.8)			260.1 (200.9)			285.3 (212.5)			357.6 (251.5)
Vegetable, g/day	237.8 (146.9)			258.4 (163.0)			267.1 (173.0)			285.2 (179.0)			344.3 (222.3)
Tea, g/day	277.1 (515.5)			258.2 (469.8)			253.5 (453.2)			254.1 (453.4)			263.4 (441.7)
Fish, g/day	14.5 (19.1)			14.3 (17.2)			14.7 (18.2)			15.4 (19.1)			17.4 (21.9)
Dairy, servings/day	1.3 (2.1)			1.4 (2.2)			1.4 (2.1)			1.4 (2.1)			1.4 (2.0)

Abbreviations: HEI, Healthy Eating Index; SD, standard deviation.
^a"Others" refers to Asian, Pacific Islander, or American Indian.
^bWeight (kg)/height (m)².
^cTotal time of moderate to vigorous physical activity per week.

Table 2. Hazard Ratios for Associations of Dietary Diabetes Risk-Reduction Score With All-Cause and Cause-Specific Mortality, a Post Hoc Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, United States, 1993–2015
Mortality Cause and the Ranges (Medians) of Quintiles of Dietary Diabetes Risk-Reduction Score	No. of Deaths	Death Rate^a	Model 1^b		Model 2^c		Model 3^d		Model 4^e
	No. of Deaths	Death Rate^a	HR	95% CI	HR	95% CI	HR	95% CI	HR	95% CI
All-cause mortality
9–19 (17)	3,774	174.13	1.00	Referent	1.00	Referent	1.00	Referent	1.00	Referent
20–22 (21)	3,870	163.31	0.89	0.85, 0.93	0.93	0.89, 0.98	0.92	0.88, 0.97	0.90	0.86, 0.93
23–24 (23)	2,721	150.81	0.82	0.78, 0.86	0.88	0.84, 0.93	0.87	0.82, 0.91	0.83	0.79, 0.87
25–27 (26)	3,451	140.11	0.75	0.71, 0.78	0.83	0.79, 0.87	0.81	0.77, 0.85	0.82	0.78, 0.86
28–40 (30)	3,716	126.41	0.68	0.65, 0.71	0.79	0.76, 0.83	0.76	0.72, 0.80	0.74	0.70, 0.78
P for trend			<0.001		<0.001		<0.001		<0.001
Cardiovascular mortality
9–19 (17)	1,044	48.17	1.00	Referent	1.00	Referent	1.00	Referent	1.00	Referent
20–22 (21)	1,040	43.89	0.86	0.79, 0.93	0.90	0.83, 0.99	0.89	0.81, 0.97	0.85	0.78, 0.92
23–24 (23)	760	42.12	0.82	0.74, 0.90	0.89	0.81, 0.98	0.86	0.79, 0.95	0.80	0.73, 0.88
25–27 (26)	968	39.3	0.75	0.68, 0.82	0.84	0.77, 0.92	0.81	0.74, 0.89	0.82	0.75, 0.90
28–40 (30)	997	33.92	0.65	0.60, 0.71	0.79	0.72, 0.87	0.73	0.66, 0.81	0.69	0.62, 0.76
P for trend			<0.001		<0.001		<0.001		<0.001
Cancer mortality
9–19 (17)	1,219	56.24	1.00	Referent	1.00	Referent	1.00	Referent	1.00	Referent
20–22 (21)	1,285	54.23	0.95	0.87, 1.02	1.00	0.92, 1.08	0.99	0.92, 1.08	0.97	0.90, 1.04
23–24 (23)	873	48.39	0.85	0.78, 0.93	0.92	0.84, 1.00	0.91	0.83, 1.00	0.89	0.81, 0.97
25–27 (26)	1,120	45.47	0.80	0.73, 0.86	0.89	0.82, 0.97	0.88	0.81, 0.96	0.90	0.83, 0.98
28–40 (30)	1,222	41.57	0.74	0.68, 0.80	0.87	0.80, 0.94	0.85	0.78, 0.94	0.83	0.76, 0.92
P for trend			<0.001		<0.001		<0.001		<0.001

Abbreviations: CI, confidence interval; HR, hazard ratio.
^aCrude death rate per 10,000 person-years.
^bAdjusted for age (years) and sex (male, female).
^cAdjustments from model 1 plus ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, others), trial arm (intervention, control), educational level (some college or below, college graduate, postgraduate), marital status (married or living as married, widowed, divorced, separated, never married), history of hypertension (yes, no), family history of cancer (yes, no; only for all-cause and cancer mortality), aspirin use (yes, no), single or multivitamin supplement use (yes, no), smoking status (current, past, never), alcohol consumption (g/day), body mass index, physical activity (minutes/week), and energy intake from diet (kcal/day).
^dAdjustments from model 2 plus consumption of fruits (g/day), vegetables (g/day), tea (g/day), fish (g/day), and dairy (servings/day).
^eAdjustments from model 2 plus consumption of fruits (g/day), vegetables (g/day), tea (g/day), fish (g/day), and dairy (servings/day), with body mass index treated as a time-varying covariate.

Table 3. Subgroup Analyses of the Association of Dietary Diabetes Risk-Reduction Score With All-Cause and Cause-Specific Mortality, a Post Hoc Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, United States, 1993–2015
Subgroup Variable	All-Cause Mortality			Cardiovascular Mortality			Cancer Mortality
Subgroup Variable	HR^a	95% CI	P for Interaction	HR^a	95% CI	P for Interaction	HR^a	95% CI	P for Interaction
Age, years			0.345			0.781			0.825
≥65	0.77	0.72, 0.81		0.71	0.64, 0.80		0.86	0.77, 0.96
<65	0.75	0.68, 0.83		0.81	0.65, 1.00		0.85	0.73, 0.99
Sex			0.280			0.024			0.032
Male	0.77	0.72, 0.83		0.81	0.71, 0.92		0.78	0.69, 0.89
Female	0.74	0.68, 0.80		0.61	0.52, 0.72		0.94	0.81, 1.08
Trial group			0.592			0.199			0.469
Intervention	0.76	0.71, 0.82		0.78	0.68, 0.90		0.84	0.74, 0.95
Control	0.76	0.71, 0.82		0.68	0.59, 0.79		0.87	0.77, 0.99
History of hypertension			0.997			0.595			0.504
Yes	0.76	0.69, 0.82		0.73	0.62, 0.85		0.82	0.70, 0.97
No	0.77	0.72, 0.82		0.74	0.65, 0.84		0.87	0.78, 0.97
Body mass index^b			0.104			0.114			0.299
≥25	0.79	0.74, 0.84		0.78	0.69, 0.88		0.88	0.79, 0.99
<25	0.72	0.66, 0.78		0.66	0.55, 0.78		0.81	0.70, 0.95
Smoking status			0.149			0.663			0.002
Current or past	0.70	0.66, 0.75		0.72	0.63, 0.81		0.73	0.65, 0.82
Never	0.77	0.71, 0.84		0.69	0.59, 0.80		1.00	0.86, 1.17
Alcohol intake, g/day^c			0.023			0.895			0.023
Heavy	0.67	0.59, 0.77		0.83	0.63, 1.10		0.65	0.51, 0.82
None, light, or moderate	0.79	0.75, 0.84		0.74	0.66, 0.82		0.90	0.81, 0.99

Abbreviations: CI, confidence interval; HR, hazard ratio.
^aHRs are for the comparison of quintile 5 to quintile 1 and are adjusted for age (years), sex (male, female), ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, others), trial arm (intervention, control), educational level (some college or below, college graduate, postgraduate), marital status (married or living as married, widowed, divorced, separated, never married), history of hypertension (yes, no), family history of cancer (yes, no; only for all-cause and cancer mortality), aspirin use (yes, no), single or multivitamin supplement use (yes, no), smoking status (current, past, never), alcohol consumption (g/day), body mass index, physical activity (min/week), energy intake from diet (kcal/day), and consumption of fruits (g/day), vegetables (g/day), tea (g/day), fish (g/day), and dairy (servings/day). In subgroup analyses stratified by sex, trial arm, history of hypertension, and smoking status, HRs were not adjusted for the stratification factor.
^bWeight (kg)/height (m)².
^cLight, moderate, and heavy alcohol consumption are defined as ≤6 g/day, >6 and <28 g/day for men and >6 and <14 g/day for women, and >28 g/day for men and >14 g/day for women, respectively.

Table 4. Association of Each Component of a Type 2 Diabetes–Prevention Diet With All-Cause and Cause-Specific Mortality, a Post Hoc Analysis of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, United States, 1993–2015
Dietary Component and Quintile Range	All-Cause Mortality			Cardiovascular Mortality			Cancer Mortality
Dietary Component and Quintile Range	No. of Deaths	HR^a	95% CI	No. of Deaths	HR^a	95% CI	No. of Deaths	HR^a	95% CI
Glycemic index
<50.09	3,453	1.00	Referent	946	1.00	Referent	1,111	1.00	Referent
50.09–52.56	3,352	0.93	0.88, 0.97	921	0.91	0.83, 1.00	1,069	0.95	0.87, 1.03
52.57–54.58	3,507	0.93	0.89, 0.98	947	0.90	0.81, 0.99	1,123	0.96	0.88, 1.05
54.59–56.93	3,418	0.89	0.84, 0.94	938	0.87	0.79, 0.96	1,160	0.97	0.88, 1.06
≥56.94	3,802	0.95	0.90, 1.01	1,057	0.94	0.85, 1.05	1,256	1.00	0.91, 1.10
P for trend		0.061			0.225			0.817
Cereal fiber, g/day
<6.60	3,944	1.00	Referent	1,074	1.00	Referent	1,283	1.00	Referent
6.60–9.27	3,559	0.90	0.86, 0.95	967	0.91	0.83, 0.99	1,177	0.94	0.86, 1.02
9.28–12.08	3,325	0.85	0.81, 0.90	944	0.90	0.81, 0.99	1,055	0.84	0.77, 0.92
12.09–16.16	3,330	0.82	0.78, 0.87	882	0.80	0.72, 0.89	1,093	0.85	0.77, 0.94
≥16.17	3,374	0.79	0.74, 0.85	942	0.80	0.70, 0.92	1,111	0.82	0.73, 0.94
P for trend		<0.001			0.001			0.003
Ratio of polyunsaturated to saturated fatty acids
<0.52	4,268	1.00	Referent	1,196	1.00	Referent	1,357	1.00	Referent
0.52–0.65	3,634	0.91	0.87, 0.95	1,012	0.88	0.81, 0.96	1,171	0.93	0.86, 1.01
0.66–0.78	3,392	0.88	0.84, 0.92	945	0.84	0.77, 0.92	1,132	0.94	0.87, 1.02
0.79–0.98	3,188	0.85	0.81, 0.90	801	0.73	0.66, 0.80	1,058	0.91	0.84, 1.00
≥0.99	3,050	0.84	0.80, 0.89	855	0.77	0.70, 0.85	1,001	0.91	0.84, 1.00
P for trend		<0.001			<0.001			0.097
Trans-fatty acids, g/day
<1.57	3,508	1.00	Referent	1,017	1.00	Referent	1,044	1.00	Referent
1.57–2.66	3,265	0.92	0.88, 0.97	914	0.90	0.82, 0.99	1,037	0.96	0.88, 1.05
2.67–3.95	3,428	0.95	0.90, 1.00	940	0.91	0.83, 1.01	1,102	0.99	0.90, 1.08
3.96–5.95	3,514	0.95	0.90, 1.00	903	0.86	0.78, 0.96	1,240	1.06	0.96, 1.17
≥5.96	3,817	0.97	0.91, 1.04	1,035	0.94	0.83, 1.07	1,296	1.02	0.90, 1.15
P for trend		0.830			0.570			0.383
Sugar-sweetened beverages, g/day
<15.94	3,519	1.00	Referent	973	1.00	Referent	1,107	1.00	Referent
15.94–48.84	3,462	0.92	0.88, 0.96	935	0.88	0.81, 0.97	1,142	0.99	0.90, 1.09
48.85–130.34	3,479	0.93	0.89, 0.98	970	0.92	0.84, 1.01	1,156	1.00	0.92, 1.09
130.35–339.08	3,521	0.97	0.93, 1.02	962	0.95	0.86, 1.04	1,128	0.99	0.91, 1.08
≥339.09	3,551	1.00	0.95, 1.05	969	0.99	0.90, 1.09	1,186	1.01	0.92, 1.10
P for trend		0.022			0.191			0.835
Nuts, g/day
<0.08	4,231	1.00	Referent	1,180	1.00	Referent	1,292	1.00	Referent
0.08–1.09	3,651	0.93	0.89, 0.97	1,021	0.94	0.86, 1.02	1,201	1.01	0.93, 1.09
1.10–3.41	3,284	0.84	0.81, 0.88	913	0.85	0.78, 0.93	1,038	0.87	0.80, 0.94
3.42–7.78	3,229	0.84	0.80, 0.88	849	0.80	0.73, 0.87	1,097	0.93	0.86, 1.01
≥7.79	3,137	0.82	0.78, 0.86	846	0.80	0.73, 0.88	1,091	0.92	0.84, 1.00
P for trend		<0.001			<0.001			0.163
Coffee, g/day
<24.17	3,307	1.00	Referent	960	1.00	Referent	948	1.00	Referent
24.17–441.20	3,454	0.91	0.87, 0.96	1,027	0.92	0.84, 1.00	987	0.94	0.86, 1.02
441.21–1,050.32	3,440	0.86	0.82, 0.90	922	0.79	0.72, 0.87	1,155	1.04	0.95, 1.13
1,050.33–1,278.36	3,360	0.83	0.79, 0.87	861	0.75	0.68, 0.83	1,200	1.03	0.94, 1.12
≥1,278.37	3,971	0.88	0.84, 0.93	1,039	0.82	0.74, 0.90	1,429	1.07	0.98, 1.17
P for trend		<0.001			<0.001			0.010
Red and processed meat, g/day
<2.19	3,212	1.00	Referent	946	1.00	Referent	900	1.00	Referent
2.19–5.01	3,246	0.96	0.91, 1.01	897	0.90	0.82, 0.99	1,041	1.09	1.00, 1.19
5.02–9.38	3,294	0.92	0.87, 0.97	861	0.81	0.74, 0.89	1,094	1.07	0.98, 1.17
9.39–18.58	3,660	0.96	0.91, 1.01	1,011	0.89	0.81, 0.98	1,266	1.16	1.06, 1.28
≥18.59	4,120	1.01	0.95, 1.07	1,094	0.89	0.80, 0.99	1,418	1.19	1.08, 1.31
P for trend		0.052			0.590			0.002

Abbreviations: CI, confidence interval; HR, hazard ratio.
^aAdjusted for age (years), sex (male, female), ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, others), trial arm (intervention, control), educational level (college below, college graduate, postgraduate), marital status (married or living as married, widowed, divorced, separated, never married), history of hypertension (yes, no), family history of cancer (yes, no; only for all-cause and cancer mortality), aspirin use (yes, no), single or multivitamin supplement use (yes, no), smoking status (current, past, never), alcohol consumption (g/day), body mass index, physical activity (min/week), energy intake from diet (kcal/day), and consumption of fruits (g/day), vegetables (g/day), tea (g/day), fish (g/day), and dairy (servings/day). All individual components were mutually adjusted, with each component treated as a continuous variable in regression models.

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Type 2 Diabetes–Prevention Diet and All-Cause and Cause-Specific Mortality

A Prospective Study

Abstract and Introduction

Abstract

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