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

Citation:

U.K. Prospective Diabetes Study Group, prepared by Manley SE, Stratton IM, Cull CA, Frighi V, Eeley A, Matthews DR, Holman RR, Turner RC, Neil HAW. Effects of three months' diet after diagnosis of type 2 diabetes on plasma lipids and lipoproteins (UKPDS 45). Diabet Med. 2000; 17: 518-523.

PubMed ID: 10972581

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 the effects of a high-carbohydrate, low-fat and high-fiber diet, with energy restriction for obese patients, on fasting plasma lipids and lipoproteins in patients with newly diagnosed type 2 diabetes.

Inclusion Criteria:

Newly diagnosed diabetic patients
Aged 25 to 65 years
Plasma glucose more than six mmol per L on two occasions after fasting.

Exclusion Criteria:

Severe vascular disease defined as more than one major vascular episode
History of myocardial infarction in the previous year
Current angina or heart failure
Accelerated hypertension
Proliferative or pre-proliferative retinopathy
Renal failure
Other life-threatening diseases such as cancer
Illness requiring systemic steroids
Uncorrected endocrine abnormality
Ketonuria suggestive of type 1 diabetes
For patients entering the study, hormone replacement therapy, oral contraceptives and thiazide diuretics were discontinued and a loop diuretic was substituted for thiazides.

Description of Study Protocol:

Recruitment: Between 1977 and 1991, local general practitioners in 23 study centers were asked to refer all newly diagnosed diabetic patients aged 25 to 65 years inclusive
Design: Randomized controlled clinical trial
Blinding used: Implied with measurements.

Intervention

At the initial visit (and subsequently at monthly intervals) patients were seen by a dietitian who had no details of their lipid status
Patients received individualized dietary advice consistent with that published by the British Diabetic Association
A hypocaloric diet was prescribed for patients with an ideal body weight of 120% or more
The aim of the diet was to obtain 50% of calories from unrefined carbohydrate, restrict the intake of rapidly absorbed monosaccharides and disaccharides and to limit fat intake to 35% of total energy by substitution of polyunsaturated for saturated fats
The intake of soluble fiber was increased by the consumption of more fruit and vegetables.

Statistical Analysis

Statistical analyses were carried out using SAS
Results were expressed as mean (SD) or geometric mean (SD interval) for data not normally distributed such as triglyceride and insulin
Changes in the variables were expressed as mean difference with 95% confidence intervals (CI) and the statistical significance assessed by paired student's T-tests
The effect of regression to the mean for tertiles of plasma lipids was estimated
For the multivariate linear regression analysis with stepwise selection, hyperlipidemia was defined as a cholesterol concentration more than 6.5mmol per L or triglyceride more than 2.2mmol per L
This analysis was used to assess the correlation of the changes in total cholesterol and triglyceride with the clinical and biochemical characteristics at presentation and the respective changes after diet.

Data Collection Summary:

Timing of Measurements

Measurements were made at diagnosis and after three months.

Dependent Variables

Biochemical measurements included plasma glucose, HbA1c, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides
Plasma glucose was measured in study centers and other measurements were performed by the coordinating laboratory
Lipid measurements in the co-ordinating laboratory were within the limits for accuracy of the lipid standardization program of the CDC.

Independent Variables

At the initial visit (and subsequently at monthly intervals) patients were seen by a dietitian who had no details of their lipid status
Patients received individualized dietary advice consistent with that published by the British Diabetic Association
A hypocaloric diet was prescribed for patients with an ideal body weight of 120% or more
The aim of the diet was to obtain 50% of calories from unrefined carbohydrate, restrict the intake of rapidly absorbed monosaccharides and disaccharides and to limit fat intake to 35% of total energy by substitution of polyunsaturated for saturated fats
The intake of soluble fiber was increased by the consumption of more fruit and vegetables.

Description of Actual Data Sample:

Initial N

A total of 7,616 patients were referred and 2,574 were excluded
5,102 patients entered the UKPDS comprised several ethnic groups but analysis was restricted to the 4,178 caucasian patients
A further 1,272 patients were excluded and 561 were randomized to pharmacological therapy and 257 remained on diet therapy
A further 454 patients were not included since lipids were not measured at the start of the UKPDS.

Attrition (Final N)
2,906 patients were included in the analysis, with a median duration of 15 weeks of dietary therapy: 1,691 men and 1,215 women.

Age
Mean age: 52.7±8.5 years for men; 53.7±8.7 years for women.

Ethnicity

100% Caucasian. The 5,102 patients entered into the UKPDS were 82% caucasian, 10% Asian Indian and 8% Afro-Caribbean but analysis was restricted to the 4,178 caucasian patients as there was insufficient data for analysis of the other ethnic groups.

Other Relevant Demographics
None mentioned.

Anthropometrics
981 (58%) men and 984 (81%) women were obese, weighing more than 120% of ideal body weight.

Location
United Kingdom.

Summary of Results:

Key Findings

Men (N=1,691)	At Diagnosis	Change After Diet	P-Value
Age (Years)	52.7 (8.5)
BMI (kg/m²)	28.6 (4.8)	-1.52 (-1.59 to -1.45)	<0.001
Weight (kg)	86.6 (15.9)	-4.61 (-4.82 to -4.40)	<0.001
Fasting Plasma Glucose (mmol/L)	11.2 (3.4)	-2.99 (-3.14 to -2.83)	<0.001
HbA1c (%)	8.9 (2.2)	-2.03 (-2.13 to -1.93)	<0.001
Fasting Plasma Insulin (mU/L)	13.1 (7.6 - 22.8)	-1.96 (-2.33 to -1.59)	<0.001
Total Cholesterol (mmol/L)	5.5 (1.0)	-0.28 (-0.33 to -0.24)	<0.001
LDL-Cholesterol (mmol/L)	3.6 (1.0)	-0.23 (-0.27 to -0.19)	<0.001
HDL-Cholesterol (mmol/L)	1.01 (0.24)	0.02 (0.01 to 0.04)	<0.001
Triglyceride (mmol/L)	1.78 (1.05 - 3.04)	-0.41 (-0.47 to -0.35)	<0.001

Women (N=1,215)	At Diagnosis	Change After Diet	P-Value
Age (Years)	53.7 (8.7)
BMI (kg/m²)	31.1 (6.5)	-1.74 (-1.82 to -1.65)	<0.001
Weight (kg)	79.4 (17.4)	-4.43 (-4.65 to -4.21)	<0.001
Fasting Plasma Glucose (mmol/L)	11.9 (3.5)	-2.93 (-3.12 to -2.74)	<0.001
HbA1c (%)	9.1 (2.1)	-1.78 (-1.89 to -1.66)	<0.001
Fasting Plasma Insulin (mU/L)	15.3 (8.9 - 26.3)	-1.93 (-2.41 to -1.46)	<0.001
Total Cholesterol (mmol/L)	5.8 (1.2)	-0.09 (-0.14 to -0.04)	<0.01
LDL-Cholesterol (mmol/L)	3.9 (1.1)	-0.09 (-0.14 to -0.04)	<0.001
HDL-Cholesterol (mmol/L)	1.09 (0.25)	0.01 (0 to 0.02)	<0.05
Triglyceride (mmol/L)	1.81 (1.12 - 2.94)	-0.23 (-0.28 to -0.18)	<0.001

Other Findings

The mean body weight at diagnosis was 83kg
Weight decreased after diet by a mean of 4.5kg; BMI decreased by 1.51kg/m²; plasma glucose fell by three mmol per L from 11mmol per L and HbA1c by 2% from 9%
Triglyceride concentrations were reduced in men by -0.41mmol per L (95% confidence interval, -0.47 to -0.35) from a geometric mean of 1.8mmol per L (1 SD interval, 1.0 to 3.0) and in women by -0.23mmol per L (-0.28 to -0.18) from a similar level
Cholesterol decreased in men by -0.28mmol per L (-0.33 to -0.24) from 5.5mmol per L (1.1) and in women by -0.09mmol per L (-0.14 to -0.04) from 5.8mmol per L (1.2) with corresponding changes in LDL-cholesterol
HDL-cholesterol increased in men by 0.02mmol per L (0.01 to 0.04) and in women by 0.01mmol per L (0 to 0.02)
Triglyceride concentration in the top tertile was reduced by 37% in men (more than 2.1mmol per L) and by 23% in women (more than 2.2mmol per L) with regression to mean accounting for 13% and 6%, respectively
Similarly cholesterol in the top tertile was reduced by 12% in men (more than 5.8mmol per L) and 7% in women (more than 6.2mmol per L), with a 6% of the decrease in both men and women accounted for by regression to the mean.

Author Conclusion:

Initial dietary therapy in patients with newly diagnosed type 2 diabetes substantially reduced plasma triglyceride, marginally improved total cholesterol and subfractions, and resulted in a potentially less atherogenic profile, although this did not eliminate the excess cardiovascular risk in patients with type 2 diabetes.

Funding Source:

Government:

UK Dept of Health, NIDDK

Industry:

Boehringer Mannheim, Novo Nordisk, Bayer, Bristol Myers Squibb, Hoechst, Lilly, Lipha, Farmitalia Carlo Erba

Pharmaceutical/Dietary Supplement Company:

Not-for-profit

UK Medical Research Council, British Diabetic Association, British Heart Foundation

Reviewer Comments:

As mentioned in the UKPDS 1990 publication, 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?	Yes
	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?		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