Diabetic Diet

Participants were excluded from the analysis if they died before the follow-up interview (n = 7,722), reported baseline diabetes (n = 5,469), cancer, heart disease, or stroke (n = 5,975), reported extreme sex-specific energy intakes (<600 or >3,000 kcal women; <700 or >3,700 kcal men), or migrated out of Singapore (n = 17). Also excluded were 20 participants whose diabetes status was not clear after the validation effort, which left 43,176 participants in the present analysis.
Dietary patterns were derived by principal component analysis (PCA) using SAS 9.1 software (SAS Institute Inc., Cary, NC). PCA in nutritional analyses aims to account for the maximal variance of dietary intake by combining the many different dietary variables into a smaller number of factors based on the intercorrelation of these variables. All 165 foods and beverages, including alcohol, were first standardized to the same frequency/month unit before the PCA method was applied and factors were extracted. The factors were rotated orthogonally to maintain an uncorrelated state and improve interpretability, and a two-factor solution was retained based on eigenvalues, scree plot, and factor interpretability. For comparability and interpretability of our results, we present factor loadings ≥0.20 even though values <0.20 are statistically significant due to the large sample size of the study. These parameters align with previous studies (5 (link)–9 (link)).
Factor scores for each participant were calculated by multiplying the intake of the standardized food item by their respective factor loadings on each pattern. The scores are linear variables and represent the weighted sum of all 165 food and beverage items. Participants were divided into quintiles by score to indicate the level at which their dietary intake corresponded with each pattern (i.e., a higher score corresponds with greater conformity to the derived pattern). Factors were initially extracted by sex, dialect, and smoking status and were highly similar in loading structure and disease prediction to the reported whole cohort factors, so the factors derived from the overall cohort were used.
Baseline and dietary characteristics were calculated for participants across quintiles of each dietary pattern score. Tests for trend across dietary pattern scores were performed by assigning the median value of the quintile to the respective categories and entering this as a continuous variable into the models. Person-years for each participant were calculated from the year of recruitment to the year of reported type 2 diabetes diagnosis, or year of follow-up telephone interview for those who did not report a diabetes diagnoses. Hazard ratios (HRs) per quintile of dietary pattern score were estimated by Cox proportional hazards regression models using the SAS statistical software. There was no evidence that proportional hazard assumptions were violated, as indicated by the lack of significant interaction between the dietary pattern scores and a function of survival time in the models.
Two models were constructed to examine the association between dietary pattern score and risk of type 2 diabetes. Covariates included in model I were baseline age (<50, 50–54, 55–59, 60–64, ≥65), year of interview (1993–1995 and 1996–1998), dialect (Hokkiens vs. Cantonese), sex, education (none, primary, secondary or higher), smoking (never, ever), any moderate or strenuous physical activity (yes vs. no), history of physician-diagnosed hypertension (yes vs. no), and total energy intake (kcal/day). Model II included these variables plus baseline BMI (kg/m² as the original BMI and its quadratic term [BMI²]) because this may represent a mediator in this diet–diabetes relationship. Analyses testing for interactions of sex, age, smoking, physical activity, and BMI with the dietary pattern scores, as well as stratification, were completed. Lastly, sensitivity analyses excluding individuals with less than 2 years of follow-up were also done to account for confounding due to antecedent disease.

Men and women with type 2 diabetes, aged 18–77 years, were enrolled between September 2007 and July 2008 at 85 sites in the U.S., Canada, Mexico, and Russia. Eligible patients were treatment-naive subjects whose hyperglycemia was inadequately controlled with diet and exercise alone. Entry criteria included BMI ≤45 kg/m² and fasting C-peptide ≥1.0 ng/ml. Patients were excluded if they had a history of type 1 diabetes, serum creatinine ≥133 μmol/l (men) or ≥124 μmol/l (women), urine albumin-to-creatinine ratio >200 mg/mmol, aspartate transaminase and/or alanine transaminase >3 times the upper limits of normal, creatine kinase ≥3 times the upper limit of normal, symptoms of severely uncontrolled diabetes (including marked polyuria and polydipsia with >10% weight loss during the last 3 months before enrollment); significant renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases, a cardiovascular event (including New York Heart Association class III/IV congestive heart failure) within 6 months of enrollment, and severe uncontrolled blood pressure (systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg).
This was a 24-week randomized, parallel-group, double-blind, placebo-controlled phase 3 trial with a 2-week diet/exercise placebo lead-in (1 week for patients with enrollment A1C 10.1–12.0%). The respective institutional review board or independent ethics committee approved the study protocol, and all patients gave informed consent. Patients with A1C 7.0–10% were randomly assigned equally to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin, administered once daily either in the morning (main cohort) or evening (exploratory cohort) for 24 weeks. Patients with A1C 10.1–12% (high-A1C exploratory cohort) were assigned randomly in a 1:1 ratio to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin (a placebo group was not included because of the high A1C levels). Patients with fasting plasma glucose (FPG) >270 mg/dl at week 4, >240 mg/dl at week 8, or >200 mg/dl at weeks 12–24 were eligible for open-label rescue medication (500 mg metformin, titrated as needed up to 2,000 mg). Patients with A1C >8.0% for 12 weeks despite a maximum tolerated metformin dose were discontinued. Throughout the study, patients received diet/exercise counseling per American Diabetes Association recommendations.