EAL

DM: Prevention of Type 2 Diabetes (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To ascertain if frequent nonvigorous physical activity, like vigorous exercise, contributes to increased insulin sensitivity.

Inclusion Criteria:

African-American, Hispanic, non-Hispanic white.

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40-69 years of age.  
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Variable glucose tolerance levels (normal, impaired, non-insulin-taking NIDDM).

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Male or female.  
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Attended at one of four centers found in California, Colorado, or Texas.

Exclusion Criteria:

None listed.

Description of Study Protocol:

Recruitment: Participants to have variable glucose tolerance levels (normal, impaired, non-insulin-taking NIDDM); variable ethnicities (African-American, Hispanic, non-Hispanic white); sex (male or female); age (40-49, 50-59, 60-69). Two centers (Los Angeles and Oakland, CA) sampled African American and non-Hispanic white members from members of a non-profit HMO. 2 centers (San Luis Valley, CO and San Antonio, TX) sampled Hispanics and non-Hispanic whites from ongoing population based epidemiologic studies. Subjects recruited between October 1992 and April 1994.

Design: Cross-Sectional Study. Prior to coming to two visits, participants were asked to fast for 12 hours, and to abstain from heavy exercise, smoking, and alcohol for 24 hours. At the first visit, participants were given a two hour 75g Oral Glucose Tolerance Test (OGTT), to establish glucose tolerance status, except those taking oral hypoglycemic meds were classed as NIDDM regardless of test results. At the second visit, a modified (injected insulin and 12 samples, not 30) Frequently Sampled Intravenous Glucose Tolerance test (FSIGT) was performed, Physical activity was assessed (total Metabolic Equivalents (METs)) by answers to previously validated questions, and by a 1-year recall, taken by centrally trained and certified interviewers (monitored by tapes). Insulin sensitivity was calculated using math modeling – the time course of plasma glucose was fit using nonlinear least squares methods, with known plasma insulin levels (method is MINMOD). Weight and height were measured, BMI calculated. Waist circumference and hip girth were measured, waist-to-hip ratio calculated. A food frequency (NCI-Health Habits and Hx questionnaire) interview was done and analyzed (HHHQ-DIETSYS Analysis Software). Interviews were done to determine diagnosis (by physician) of diabetes, use of medication, smoking status, and intake of alcohol.

Blinding Used (if applicable): N/A

Intervention (if applicable): N/A

Statistics: Quintiles of physical activity were assessed in terms of insulin sensitivity. Linear regression was performed which included variables (total, vigorous, non-vigorous EEE) to evaluated study hypotheses. Regression analysis assumed a normal distribution. Fifteen percent of sample had insulin sensitivity of 0 secondary to limits of FSIGT computations, and the distribution was right skewed, thus the natural log of insulin sensitivity plus one was calculated, to achieve normality. Covariates included age, sex, ethnicity, clinical center, smoking status, alcohol intake, percent fat calories, use of antihypertensive meds. BMI and WHR were added to models to evaluate any association between physical activity and insulin sensitivity to assure independence of obesity and fat distribution. Data were further evaluated to consider diabetes status, ethnicity, and sex. All analysis used SAS software.

Data Collection Summary:

Timing of measurements: At second visit, blood was collected at -5, 2, 4, 8, 19, 22, 30, 40, 50, 70, 100, and 180 min.

Dependent Variables:

Plasma glucose measured in duplicate using glucose oxidase autoanalyzer technique
Plasma insulin determined by radioimmunoassay

Independent variables:

At second visit, 50% glucose (0.3 g/kg of body weight), and regular human insulin (0.03 U/kg), were injected at 0 and 20 min, respectively.

Control variables:

Comparative validity study with n=55 participants (11 normal glucose, 20 impaired glucose tolerance, 24 NIDDM) using glucose clamp technique (r=0.55, P<.001).

Description of Actual Data Sample:

Initial N: Goal was 1600

Attrition (final N): 1467

Age: 40-69

Ethnicity: African-American, Hispanic, non-Hispanic white

Other relevant demographics: None

Anthropometrics: See table below.

Location: 4 centers: Los Angeles and Oakland, CA, San Luis Valley, CO, and San Antonio, TX

Sample characteristics of all study participants.

Characteristics	All participants (n=1467)	Subset with no vigorous exercise (n=446)
Age, mean (SD), y	55.6 (8.5)	57.8 (8.2)
BMI, mean (SD), kg/sq meter	29.3 (5.8)	30.3 (6.5)
WHR, mean (SD)	0.88 (0.09)	0.87 (0.09)
Insulin sensitivity - mean (SD) min(-1) times micro U( –1) times microL(-1) X (10-4)	1.7 (1.9)	1.3 (1.5)
Fasting insulin, mean (SD), pmol/L	131.3 (112.6)	144.9 (120.5)
Men/women, % of participants	45/55	27.73
Diabetes status, % of participants Normal	46	36
IGT	22	27
NIDDM	32	37
Race/ethnicity, % of participants Non-Hispanic white	38	32
Hispanic	28	29
African American	34	39
Time spent in activities (one yr recall) % of time Sleep (MET=1.0)	28	28
Light (MET=1.5)	63	66
Moderate (MET=3.5-5)	7	6
Vigorous (MET = or > 6)	2	0

Summary of Results:

Adjusted value of insulin sensitivity and fasting insulin according to frequency of participation in vigorous activity.

Participation in vigorous activities	Insulin sensitivity Min(-1) X micro U (–1) X microL(-1) X (10-4) (95% CI)	Fasting insulin, pmol/L (95% CI)
Rarely or never (n=485)	0.90 (0.83-0.97)	113.86 (104.40-123.33)
1-3 times/mo (n=290)	1.12 (1.02-1.22)	109.34 (98.79-119.89)
1 time/wk (n=179)	1.38 (1.23-1.53)	101.66 (89.11-114.22)
2-4 times/wk (n=381)	1.43 (1.31-1.55)	92.98 (84.95-101.02)
5 times/wk (n=132)	1.59 (1.39-1.79)	83.87 (71.61-96.14)

After adjustment for confounders, frequency of participation in vigorous activities positively associated with insulin sensitivity (p<.001). Inverse association for vigorous activity related to fasting insulin (p<.001).

Additional data reveal a positive association between physical activity and insulin sensitivity (p<.001).

Percentage difference in insulin sensitivity associated with an estimated EEE of 836.8 kJ/d (200 kcal/d) for a 70 kg individual.

% Difference in insulin sensitivity (95% CI)

% Difference in fasting insulin (95% CI)

Model 1

Total EEE

2.68 (1.48 to 3.90)

1.87 (0.88 to 2.87

-1.95 (-3.30 to -0.60)

-1.06 (-2.21 to 0.12)

Model 2

Vigorous EEE

2.59 (1.21 to 4.00)

1.94 (0.79 to 3.10)

-2.26 (-3.80 to -0.69)

-1.47 (-2.81 to -0.12)

Nonvigorous EEE

2.88 (1.01 to 4.78)

1.73 (0.19 to 3.29)

-1.32 (-3.40 to 0.81)

-0.19 (-2.01 to 1.66)

Model 3

Total (nonvigorous)

4.69 (1.30 to 8.01)

1.98 (-0.65 to 4.69)

-3.14 (-7.35 to 1.27)

0.02 (-3.61 to 3.79)

Percentage difference in insulin sensitivity associated with an estimated EEE of 836.8 kJ/d (200 kcal/d) for a 70 kg individual, according to diabetes status, ethnicity, and sex

	Model 1	Model 2	Model 2
Categories	Total EEE % Difference in Si (95% CI)	Vigorous EEE % Difference in Si (95% CI)	Non-vigorous EEE % Difference in Si (95% CI)
Diabetes status With diabetes	1.49 (-0.14 to 3.15)	0.86 (-1.06 to 2.82)	2.64 (0.11 to 2.64)
Without diabetes	1.59 (0.26 to 2.93)	1.53 (0.97 to 5.98)	1.71 (-0.35 to 3.81)
P values	.68	.53	.93
Ethnicity Non-Hispanic white	3.17 (1.05 to 5.34)	3.45 (0.97 to 5.98)	2.61 (-0.69 to 6.01)
African-American	0.56 (-1.39 to 2.55)	0.38 (-1.76 to 4.81)	1.09 (-2.14 to 4.42)
Hispanic	4.43 (2.30 to 6.60)	4.52 (1.91 to 7.18)	4.30 (1.23 to 7.47)
P values	.07	.11	.42
Sex Women	2.26 (0.34 to 4.22)	2.17 (-0.74 to 5.16)	2.33 (-0.01 to 4.85)
Men	2.85 (1.29 to 4.44)	2.71 (1.07 – 4.38)	3.55 (0.66 to 6.33)
P values	.72	.93	.50

Author Conclusion:

Significantly higher insulin sensitivity was associated with increased participation in non-vigorous physical activity (walking), along with overall and vigorous physical activity.

Funding Source:

Government:

NIH, NHLBI

Reviewer Comments:

One-third of the subjects rarely or never participated in vigorous physical activity, but 31% participated in vigorous physical activity 2 - 5 times/week. Some of the details of the study were not included in this manuscript since other papers have been published from this study.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	Yes
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	N/A
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes