EAL

DM: Effectiveness of MNT Provided by RD/RDN (2015)

Citation:

U.K. Prospective Diabetes Study (UKPDS) 7. Response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients. Metabolism, 1990; 39: 905-912.

PubMed ID: 2392060

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To assess in which patients diet is most effective and whether one could predict the fasting plasma glucose response to a given weight loss, as well as to assess the degree to which this weight loss needs to be maintained over the subsequent year in order to maintain a near-normal plasma glucose concentration.

Inclusion Criteria:

Newly presenting patients aged 25 to 65 years
Fasting plasma glucose of greater than 6.0mmol per L on two occasions.

Exclusion Criteria:

Ketonuria
History of myocardial infarction in the previous year
Angina
Heart failure
More than one major vascular episode
Serum creatinine greater than 175mcmol per L
Severe retinopathy requiring photocoagulation
Accelerated hypertension
Uncorrected endocrine abnormality
Occupation that would not allow randomization to insulin therapy (e.g., heavy goods vehicle driver)
Severe pre-existing illness likely to limit life (e.g., cancer) or requiring extensive systemic treatment (e.g., ulcerative colitis)
Inadequate comprehension to allow cooperation
If reasonable, diuretics and estrogen therapy were stopped before assessment.

Description of Study Protocol:

Recruitment: In 15 centers, newly presenting patients meeting inclusion criteria were referred for inclusion in the study
Design: Randomized controlled trial
Blinding used: Implied with measurements.

Intervention

All patients were advised to follow the British Diabetic Association recommendations of a diet containing 50% carbohydrate, 30% fat and 20% protein, with energy restricted according to the patient's obesity and activity
The mean prescribed diet was 1,361kcal:
- Mean 1,672kcal for those patients less than 110% ideal body weight
- Mean 1,361kcal for patients 110% to 129% ideal body weight
- Mean 1,217kcal for patients 130% to 149% ideal body weight
- Mean 1,098kcal for patients greater than 150% ideal body weight.
After three months, if the mean fasting glucose was greater than 6.0mmol per L, the patient was entered into the mean randomization and allocated to either sulphonylurea, metformin or insulin therapy or to continue on diet alone. If the mean fasting glucose was less than 6.0mmol per L, patients were regarded as diet satisfactory and remained on diet alone. If the mean fasting glucose remained greater than 15.0mmol per L or they had symptoms of hyperglycaemia such as polydipsia, polyuria or excessive tiredness, the patients were regarded as primary diet failures and were randomly allocated to sulphonylurea, metformin or insulin therapy.
Centers had different availability of dietetic advice. Before the results were available, three centers had been categorized as above average in this respect, as they had additional, specific dietetic personnel for the patients in the study, 10 centers as average with advice from routine National Health Service dietitians and two centers below average, sometimes having lack of continuity of care from a single dietitian.

Statistical Analysis

Weight loss achieved over three months and the decrease in fasting plasma glucose was assessed for each center
Data analysis was performed using SPSS
Regression analyses were performed after checking that the data was normally distributed.

Data Collection Summary:

Timing of Measurements

At each clinic visit, a fasting plasma glucose was taken and the patient weighed
Patients were seen at one-month intervals for three months.

Dependent Variables

Fasting plasma glucose measured by glucose-oxidase method
Weight.

Independent Variables

All patients were advised to follow the British Diabetic Association recommendations of a diet containing 50% carbohydrate, 30% fat and 20% protein with energy restricted according to the patient's obesity and activity.
The mean prescribed diet was 1,361kcal:
- Mean 1,672kcal for those patients less than 110% ideal body weight
- Mean 1,361kcal for patients 110-129% ideal body weight
- Mean 1,217kcal for patients 130-149% ideal body weight
- Mean 1,098kcal for patients greater than 150% ideal body weight.

Description of Actual Data Sample:

Initial N

3,044 patients
59% male
41% female.

Attrition (Final N)

2,597 patients who were on a diet for three months before therapy decision
447 (15%) primary diet failures were excluded
The change in fasting plasma glucose and body weight in 823 patients who continued on diet alone for a further year after therapy decision were assessed, which included the 482 diet satisfactory patients who had a fasting plasma glucose less than 6.0mmol per L and were continued on diet and the 341 patients who had a value greater than 6.0mmol per L and were allocated to diet in the main randomization.

Age
Five to 65 years; mean, 52±8 years.

Ethnicity
Not reported.

Other Relevant Demographics
Not reported.

Anthropometrics
Mean body weight, 130±26% ideal body weight.

Location
United Kingdom.

Summary of Results:

Key Findings

Main Randomization	% IBW at Diagnosis	% IBW After 3 Months	% IBW After Further Year	FPG at Diagnosis	FPG After 3 Months	FPG After Further Year
All Patients at 1 Year (341; mean age, 53±8 years)	130±26	123±24	124±24	11.7±3.2	8.5±1.8	9.2±2.7
FPG <6 mmol/L at 1 Year (26; mean age, 53±9 years)	132±20	122±16	118±15	10.4±4	6.9±0.6	5.6±0.3
FPG >6 mmol/L at 1 Year (315; mean age, 53±8 years)	130±26	123±25	124±25	11.8±3.1	8.6±1.8	9.5±2.6

Diet Satisfactory	% IBW at Diagnosis	% IBW After 3 Months	% IBW After Further Year	FPG at Diagnosis	FPG After 3 Months	FPG After Further Year
All Patients at 1 Year (482; mean age, 52±8 years)	132±25	121±22	121±22	10.0±3.3	5.8±0.7	6.2±1.4
FPG <6 mmol/L at 1 Year (260; mean age, 51±9 years)	133±26	121±22	118±20	9.7±3.4	5.6±0.7	5.4±0.5
FPG >6 mmol/L at 1 Year (222; mean age, 52±8 years)	132±24	121±22	123±24	10.2±3.2	6.0±0.6	7.1±1.6

Other Findings

Weight decreased from 130±26% to 123±24% of ideal body weight and fasting plasma glucose decreased from 11.4±3.3mmol to 8.1±1.8mmol per L
The body weight decrease was most in the first month and in the heaviest patients, who were usually prescribed the most restricted diets
The initial fasting plasma glucose had no effect on the degree of weight loss
The decrease in fasting plasma glucose was also greatest in the first month after presentation, with a continued reduction over the next two months
The reduction in the fasting plasma glucose was greater in those presenting with high initial fasting plasma glucose (R=0.76, P<0.001) and in those who lost more weight (partial correlation coefficient R=0.19, P<0.001), but was not related to the degree of obesity
By stepwise regression analysis, 31% of the variation of the decrease in fasting plasma glucose over the first three months was accounted for by the initial fasting plasma glucose, a further 8% by the weight loss over three months, with no contribution from the initial weight
Weight loss in patients in the individual centers was proportional to the degree of availability of dietetic advice and was also associated with the degree to which the fasting plasma glucose decreased over three months
There was considerable variation in the response to dieting, but on average, patients presenting with a fasting plasma glucose of 10mmol to 12mmol per L needed to lose 28% ideal body weight (18kg) to attain a fasting plasma glucose less than 6.0mmol per L
16% of all patients achieved a near-normal (less than 6.0mmol per L) fasting plasma glucose after three months of dieting, ranging from 50% of those presenting with fasting plasma glucose of 6.0mmol to 8.0mmol per L to 10% of those with fasting plasma glucose of 16mmol to 22mmol per L
In those who achieved less than 6.0mmol per L, in the second three months the fasting plasma glucose increased by a mean of 0.4mmol per L even though there was a further mean weight reduction of 2.1% ideal body weight (1.4kg) in addition to their loss of 11.6% ideal body weight (8 kg) in the initial three months, confirming the decrease in fasting plasma glucose is determined more by the restriction of energy intake than by the body weight
Those who maintained their fasting plasma glucose at less than 6.0mmol per L in the year following the initial three-month dietary period lost a further 3% (2.0kg) ideal body weight
On average, to achieve a fasting plasma glucose of less than 6.0mmol per L, a weight loss of 16% ideal body weight was needed if the initial fasting plasma glucose was in the range of 6.0 to 8.0mmol per L, a weight loss of 21% ideal body weight for an initial fasting plasma glucose of 8.0mmol to 10mmol per L, 28% ideal body weight loss for 10mmol to 12mmol per L, 35% ideal body weight loss for 12mmol to 14mmol per L and 41% ideal body weight loss for an initial fasting plasma glucose over 14.0mmol per L
14% of all patients who presented maintained a fasting plasma glucose less than 6.0 mmol per L after the subsequent year's diet (15 months of dieting in all). On average, they had slightly lower fasting plasma glucose at presentation and had lost more weight than other patients. Of the main randomization patients who had a fasting plasma glucose more than 6.0mmol per L after three months on diet, only 8% were able to maintain less than 6.0mmol per L after a subsequent year's diet. They were patients who had fasting plasma glucose values just above 6.0mmol per L after the three months' dieting and then continued to lose, on average, a further 4% ideal body weight.

Author Conclusion:

The degree of obesity on presentation made little difference to the fasting plasma glucose response to diet, which was greater in those patients presenting with high fasting plasma glucose and in those who lost most weight on dieting
This study shows that considerable dietary restriction and weight loss is needed in most patients if the fasting plasma glucose is to be reduced to less than 6.0mmol per L
The data confirm the value of dieting, but in view of the large weight loss and equivalent large reduction in energy intake required in most patients, it is not surprising that few patients achieve near-normal fasting plasma glucose concentrations by diet alone.

Funding Source:

Government:

NIDDK, Dept of Health and Social Security

Industry:

Lilly, Novo, Hoechst, Lipha

Pharmaceutical/Dietary Supplement Company:

Not-for-profit

Medical Research Council, British Diabetic Association, British Heart Foundation, US National Eye Institute

Reviewer Comments:

Centers had different availability of dietetic advice.

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.)	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?	N/A
	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?	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.)	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?		No
	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?	???
	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?	N/A
	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?	No
	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)?	N/A
	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