EAL

PDM: Prediabetes (2013)

Citation:

Lu YH, Lu JM, Wang SY, Li CL, Zheng RP, Tian H, Wang XL. Outcome of intensive integrated intervention in participants with impaired glucose regulation in China. Adv Ther. 2011; 28(6): 511-519.

PubMed ID: 21533568

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To observe the effect of intensive integrated interventions, including therapy for hyperglycemia, hypertension, dyslipidemia, overweight or obesity and anticoagulation in a group of Chinese adults with impaired glucose regulation (IGR)
To assess its effect on diabetes prevalence.

Inclusion Criteria:

Diagnosed with IGR according to the American Diabetes Association (ADA) criteria of 2003, after administration of the 75g oral glucose tolerance test (OGTT)
If they were diagnosed with IGR, they received lifestyle and health education for one year. If they had IGR still after that year of health education, they were recruited for the present study.
Additional criteria:
- Age 40 to 80 years
- BMI 19kg/m² or more.

Exclusion Criteria:

Pregnant or lactating women
Those of childbearing potential without a medically approved method of contraception
Participants already diagnosed with type 2 diabetes mellitus (T2DM)
Presence of major debilitating diseases
Any major cardiovascular event within the past six months
Treatment with systemic glucocorticoids within the past three months
Diagnosed with any emotional disorder
Substance abuse.

Description of Study Protocol:

Design

Randomized controlled trial.

Blinding Used

Implied with measurements.

Intervention

Participants were stratified according to their condition:
- Isolated impaired glucose tolerance [I-IGT]
- Isolated impaired fasting glucose [I-IFG]
- Impaired fasting glucose combined with impaired glucose tolerance [IFG/IGT]
They were then randomized to receive either:
- Routine care (control group): Health (diabetic) education and follow-up once per year
- Intensive integrated intervention:
  - I-IGT received acarbose (50mg three times daily), dispensed every three months
  - I-IFG or IFG/IGT received metformin (0.25g three times daily), dispensed every three months
  - Participants with hypertension also received anti-hypertension agents
  - Those with dyslipidemia received antidyslipidemia agents and aspirin (100mg once daily) except where contraindicated
  - All intensive intervention group also received lifestyle intervention face-to-face once every three months and by phone once per month
    - Lectures on diet
    - Exercise
- Both groups (participants who did not have T2DM) came to the study site after an overnight fast; 75g OGTT performed each year (all medications were held the morning of the OGTT)
  - If polydipsia, polyuria or polyphagia appeared, an FPG test was performed
  - If FPG was 7.0mmol per L or more or a two-hour PG was 11.1mmol per L or more, the FPG test was repeated or a 75g OGTT was performed
  - If this reached the criteria for T2DM, it was considered a major endpoint
- Epidemiology questionnaires administered for both groups to obtain information on:
  - Demographics
  - Personal and family medical history
  - Lifestyle risk factors
- Additional assessments included:
  - Waist and hip circumference measurements
  - Blood pressure
  - Diet
  - Exercise
  - Drug therapy adjustments (changes in medications).

Statistical Analysis

All analyses were performed using the International Business Machine Corporation (IBM) Statistical Product and Service Solutions (SPSS version 11.5, Somers, NY, USA)
Insulin-related parameters was performed using log-transformed data:
- Any differences between groups calculated using a T-test
- Differences across multiple subgroups calculated by analysis of variance (ANOVA)
Any differences before and after intervention were analyzed by analysis of covariance (ANCOVA) with the relevant baseline variables as covariates
Percentage difference was analyzed using chi-square test
Risk factors associated with the progression from prediabetes to diabetes were assessed by a logistic regression analysis
P<0.05 were considered statistically significant.

Data Collection Summary:

Timing of Measurements

The control group was seen once per year
Intensive integrated intervention
- Medications were dispensed every three months
- Received lifestyle intervention face-to-face once every three months and by phone once per month.

Dependent Variables

Risk of progression from prediabetes to diabetes: Assessed by a logistic regression analysis
Variance before and after intervention of BMI
Waist circumference
Systolic blood pressure (SBP)
Diastolic blood pressure (DBP)
Total cholesterol
Triglycerides
High density lipoprotein cholesterol (HDL-C)
Homeostasis model assessment of insulin resistance (HOMA-IR) = FPG x fasting insulin (FINS)/22.5
Homeostasis model of assessment of β cell function (HBCI) = 20 x FINS/(FPG-3.5)
HBCI/insulin resistance (HBCI/IR) = HBCI/HOMA-IR.

Independent Variables

Routine care (control group): Health (diabetic) education and follow-up once per year
Intensive integrated intervention:
- I-IGT received acarbose (50mg three times daily), dispensed every three months
- I-IFG or IFG/IGT received metformin (0.25g three times daily), dispensed every three months
- Participants with hypertension also received anti-hypertension agents
- Those with dyslipidemia received antidyslipidemia agents and aspirin (100mg once daily) except where contraindicated
- All intensive intervention group also received lifestyle intervention face-to-face once every three months and by phone once per month
  - Lectures on diet
  - Exercise.

Control Variables

Age
Sex.

Description of Actual Data Sample:

Initial N

Of the 2,344 adults screened, 463 had IGR
210 had IGR after one year of health and lifestyle education and were recruited for the study
106 were randomized to receive integrated intervention
- 10 were lost to follow-up for uncertain reasons
- One discontinued due to a gastrointestinal reaction after taking metformin
- Dropout rate was 10.4%
104 were initially in the control group
- Two went abroad
- 15 were lost for uncertain reasons
- One died due to aplastic anemia
- Dropout rate was 17.3% (P=0.145).

Attrition (Final N)

Intervention group: N=95
Control Group: N=86.

Age

Intervention group: 62.44±9.16 years
Control group: 64.72±7.93 years.

Ethnicity

Chinese.

Other Relevant Demographics

	Intervention Group-Baseline	Control Group-Baseline
Sex (m/f)	50/45	45/41
Body weight (kg)	72.24±11.16	71.45±12.44
BMI (kg/m²)	27.07±3.30	26.92±3.65
Waist circumference (cm)	93.91±8.26	91.22±9.24
SBP (mm Hg)	129.65±16.86	130.06±19.54
DBP (mm Hg)	78.95±9.49	78.83±10.79
HDL-C (mmol per L)	1.23±0.25	1.26±0.24
LDL-C (mmol per L)	3.01±0.63	2.94±0.57
TC (mmol per L)	5.09±0.80	4.98±0.92
TG (mmol per L)	2.10±1.19	2.14±1.10
FPG (mmol per L)	5.89±0.43	5.96±0.51
Two-hour PG (mmol per L)	8.32±1.35	8.53±1.16
HbA1c (%)	5.91±0.34	5.98±0.43
FINS (mU per L)	9.08±4.31	8.89±4.84
Two-hour INS (mU per L)	90.06±62.83	93.40±58.89
HOMA-IR	2.17±1.10	2.09±1.37
HBCI	88.54±45.32	90.27±47.65
HBCI per IR	42.60±13.08	46.58±17.19

Anthropometrics

No significant differences in age or sex between the two groups. No significant difference between the two groups for the percentage of participants reaching target sets.

Location

Adults were from four communities of the Shijingshan District, Beijing, China.

Summary of Results:

Key Findings

	Intervention Group: Baseline	Intervention Group: Two Years	Control Group: Baseline	Control Group: Two Years	P Value
Body weight (kg)	72.24±11.16	69.58±11.40	71.45±12.44	69.97±12.90	0.013
BMI (kg/m²)	27.07±3.30	26.24±3.86	26.92±3.65	26.67±3.66	0.047
Waist circumference (cm)	93.91±8.26	89.39±9.28*	91.22±9.24	89.71±9.15	0.019
SBP (mm Hg)	129.65±16.86	126.16±17.45	130.06±19.54	143.83±23.75*	0.000
DBP (mm Hg)	78.95±9.49	73.93±9.19*	78.83±10.79	80.25±13.11	0.000
HDL-C (mmol per L)	1.23±0.25	1.52±0.31*	1.26±0.24	1.47±0.35*	0.687
LDL-C (mmol per L)	3.01±0.63	2.84±0.66	2.94±0.57	2.79±0.66	0.465
TC (mmol per L)	5.09±0.80	5.16±0.85	4.98±0.92	5.19±0.95	0.671
TG (mmol per L)	2.10±1.19	1.75±0.87*	2.14±1.10	2.05±0.80	0.038
FPG (mmol per L)	5.89±0.43	5.77±0.47	5.96±0.51	5.99±0.88	0.046
Two-hour PG (mmol per L)	8.32±1.35	6.69±1.72*	8.53±1.16	7.88±2.28*	0.032
HbA1c (%)	5.91±0.34	5.72±0.37*	5.98±0.43	5.87±0.60	0.265
FINS (mU per L)	9.08±4.31	7.53±4.84*	8.89±4.84	8.94±4.70	0.003
Two-hour INS (mU per L)	90.06±62.83	60.40±41.52*	93.40±58.89	75.72±54.15*	0.043
HOMA-IR	2.17±1.10	2.09±1.27	2.09±1.37	2.30±1.38	0.024
HBCI	88.54±45.32	77.62±46.22	90.27±47.65	73.64±46.64*	0.095
HBCI/IR	42.60±13.08	49.97±16.98*	46.58±17.19	35.67±15.47*	0.018

*P<0.05 vs. baseline at two years for each group by analysis of covariance.

Logistic regression analysis showed:

An increase in waist circumference and SBP was positively related to the progression of prediabetes to T2DM
Improvement in islet beta cell function was negatively related to the progression of prediabetes to T2DM.

Other Findings

Compliance of diet control and exercise, and adherence to anti-hypertensive medications and aspirin were significantly higher in the intensive integrated interventions group compared with the control group (P<0.05)
After two years, the success rates for achieving target plasma glucose, blood pressure, BMI and TG were significantly higher for the intensive integrated intervention group, compared with the control group (P<0.05)
After the first year of follow-up, none of the participants in the intensive integrated intervention group had developed T2DM, whereas six participants in the control group had progressed to T2DM
At two years, none of the participants in the metformin subgroup had developed T2DM, whereas five participants in the control group had progressed to T2DM
The percentage of participants who achieved a normal glucose tolerance (NGT) was higher in the metformin group compared with the control group (17.4% vs. 9.8%, P>0.05)
No participants in the acarbose group developed T2DM, whereas three participants in the corresponding control group progressed to T2DM
The proportion of participants who achieved a NGT was also higher in the acarbose group than those in the control group (40.8% vs. 33.3%, P>0.05).

Author Conclusion:

This study showed that intensive integrated intervention can significantly decrease the progression of prediabetes to diabetes, and can increase the conversion rate of prediabetes to NGT. Moreover, it could also decrease morbidity associated with different metabolic risk factors. Intensive integrated intervention could relieve insulin resistance and ameliorate islet beta cell function.

Funding Source:

Other:

not disclosed in the article

Reviewer Comments:

The only limitations mentioned in the conclusion:
- The number of participants with prediabetes was relatively small
- Duration of the study was relatively short
- Longer follow-up is needed
Reviewer comments:
- Although the article states that diet and exercise information was collected, none of that data was disclosed. It would have been interesting to see the diet composition compared in the two groups.

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?	???
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)	???
	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.)	Yes
	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?	N/A
	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.)	N/A
	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?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
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?	Yes
	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.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	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?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	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)?	N/A
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???