The best dietary balance of fatty acids, protein, and carbohydrate in patients with both glucose and lipid metabolism disorders remains unclear (1). Substitution of carbohydrates for saturated fatty acids frequently leads to increased triglyceride and decreased HDL cholesterol (2), adverse effects not seen with increased dietary monounsaturated fatty acids (MUFAs) (3). Moderate hyperglycemia can contribute to increased turnover of protein, suggesting increased need for protein in type 2 diabetes (4).

Between January 2000 and February 2001, we randomized 35 patients with the metabolic syndrome or type 2 diabetes to the contemporary American Heart Association (AHA) diet (15% of calories from protein, 30% fat, and 15% MUFAs) or a diet higher in protein, total fat, and MUFAs (25, 40, and 22% of calories, respectively; HiPro-HiMono diet). Enrollment criteria for the 42-week trial were BMI ≥25 kg/m2, elevated fasting glucose (6.1–6.9 mmol/l [110–125 mg/dl] for impaired fasting glucose and ≥6.9 mmol/l [≥126 mg/dl] for diabetes), calculated LDL cholesterol >2.8 mmol/l, and fasting triglyceride ≥1.7 mmol/l. (The trial preceded the National Cholesterol Education Program’s clinical definition of the metabolic syndrome.) These risk factors were also the trial end points.

Patients were given a scale to weigh portions and prepared their own food, with the exception of almonds, which were given to the HiPro-HiMono group to replace other primary sources of MUFAs during the last 24 weeks. All patients were taught their diet and to self-monitor food intake and weight by using password-protected web pages with individualized meal plans, menus, and messages from a dietitian.
Twelve patients withdrew within 6 weeks (because of inability to attend clinic, computer problems, and/or health reasons). An additional six patients had one to two missing observations during the follow-up period. Multilevel models were used to describe the dietary effects and permitted the use of all collected data in the statistical analyses, including incomplete cases. At 42 weeks, although trends in risk factors slightly favored the HiPro-HiMono diet, changes were not significantly different between the AHA and HiPro-HiMono groups for weight (−5.9 vs. −9.1 kg; P = 0.768), triglyceride (−0.8 vs. −1.1 mmol/l; P = 0.920), fasting glucose (−2.2 vs. −3.2 mmol/l; P = 0.153), and LDL cholesterol (0.23 vs. 0.18 mmol/l; P = 0.217). The preponderance of patients improved their glycemic control. At 42 weeks, glycemic control was normalized in all 10 patients with impaired fasting glucose; it was also normalized in 2 and reduced to impaired fasting glucose in 3 of 7 patients with diabetes. Food record analyses to evaluate compliance showed that changes from the baseline diets to assigned levels of carbohydrate and total, saturated, and monounsaturated fats were significantly different between the groups, in keeping with different dietary goals. In a similar study (5), with slightly different diets, subjects at the end of 18 months were consuming diets of similar composition.

Our long-term study, enabled by our Internet Management System, was limited by small sample size. The power to detect a 10% difference between groups at α = 0.05 with the observed SDs was <18% for LDL cholesterol, triglyceride, and fasting glucose. Weight loss was a potential confounding factor in the analyses. Nevertheless, the study’s trends support the hypothesis that a diet high in protein and MUFAs may be advantageous in correcting glucose and lipid metabolism abnormalities. Large, randomized, multicenter trials are needed.