Participants were recruited from the Durham Veterans Affairs Medical Center (VAMC) outpatient clinics. Inclusion criteria were age 35–75 years; body mass index (BMI) >25 kg/m2; and fasting serum glucose >125 mg/dL or hemoglobin A1c >6.5% without medications, or treatment with oral hypoglycemic agents (OHA) and/or insulin. Exclusion criteria were evidence of renal insufficiency, liver disease, or unstable cardiovascular disease by history, physical examination, and laboratory tests. All participants provided written informed consent approved by the institutional review board. No monetary incentives were provided.
At the first visit, participants were instructed how to follow the LCKD as individuals or in small groups, with an initial goal of ≤20 g carbohydrate per day. Participants were taught the specific types and amounts of foods they could eat, as well as foods to avoid. Initially, participants were allowed unlimited amounts of meats, poultry, fish, shellfish, and eggs; 2 cups of salad vegetables per day; 1 cup of low-carbohydrate vegetables per day; 4 ounces of hard cheese; and limited amounts of cream, avocado, olives, and lemon juice. Fats and oils were not restricted except that intake of trans fats was to be minimized. Participants were provided a 3-page handout and a handbook  detailing these recommendations. Participants prepared or bought all of their own meals and snacks following these guidelines.
In addition, on the day the diet was initiated, diabetes medications were reduced – generally, insulin doses were halved, and sulfonylurea doses were halved or discontinued. Due to the possible diuretic effects of the diet soon after initiation, diuretic medications were discontinued if of low dosage (up to 25 mg of hydrochlorothiazide or 20 mg of furosemide) or halved if of higher dosage. Participants were also instructed to take a standard multivitamin and drink 6–8 glasses of water daily, and were encouraged to exercise aerobically for 30 minutes at least three times per week.
Participants returned every other week for 16 weeks for further diet counseling and medication adjustment. When a participant neared half the weight loss goal or experienced cravings, he or she was advised to increase carbohydrate intake by approximately 5 g per day each week as long as weight loss continued. Participants could choose 5 g carbohydrate portions from one of the following foods each week: salad vegetables, low-carbohydrate vegetables, hard or soft cheese, nuts, or low-carbohydrate snacks. Diabetes medication adjustment was based on twice daily glucometer readings and hypoglycemic episodes, while diuretic and other anti-hypertensive medication adjustments were based on orthostatic symptoms, blood pressure, and lower extremity edema.
Participants completed take-home food records (4 consecutive days, including a weekend) collected at baseline and at weeks 2, 8, and 16 during the study. Participants were given handouts with examples of how to complete the records. A registered dietician analyzed the food records using a nutrition software program (Food Processor SQL, ESHA Research, Inc., Salem, OR).
The following measurements were made every other week: anthropometric and vital sign measurements; urine testing for ketones; and assessment for hypoglycemic episodes and other symptomatic side effects. Weight was measured on a standardized digital scale while the participant was wearing light clothes and shoes were removed. Skinfold thickness was measured at 4 sites – the average of 2 measurements at each site was entered into an equation to calculate percent body fat . Waist circumference was measured at the midpoint between the inferior rib and the iliac crest using an inelastic tape; 2 measurements were averaged in the analysis. Blood pressure and heart rate were measured after the participant had been seated quietly without talking for 3 minutes. Certified laboratory technicians assessed urine ketones from a fresh specimen using the following semi-quantitative scale: none, trace (up to 0.9 mmol/L [5 mg/dL]), small (0.9–6.9 mmol/L [5–40 mg/dL]), moderate (6.9–13.8 mmol/L [40–80 mg/dL]), large80 (13.8–27.5 mmol/L [80–160 mg/dL]), large160 (>27.5 mmol/L [160 mg/dL]). Hypoglycemic episodes and symptomatic side effects were assessed by direct questioning of the participant and by self-administered questionnaires.
Blood specimens were obtained at weeks 0, 8, and 16 after the participant had fasted overnight. The following serum tests were performed in the hospital laboratory using standardized methods: complete blood count, chemistry panel, lipid panel, thyroid-stimulating hormone, and uric acid. A non-fasting specimen was also drawn at weeks 4 and 12 to monitor electrolytes and kidney function.
The primary outcome was the change from baseline to week 16 in hemoglobin A1c. Changes in all variables were analyzed by the paired t-test or Wilcoxon signed-ranks test, as appropriate. Linear regression analysis was used to examine predictors of change in hemoglobin A1c. A p value of 0.05 or less was considered statistically significant. Statistical analysis was performed using SAS version 8.02 (SAS Institute, Cary, NC).