Comparing Two Low-Carbohydrate Diets With a Standard Diet in Type 2 Diabetes

This is a three-arm, open-label, randomized controlled trial conducted at a diabetes clinic in Tehran, Iran. Eligible patients - adults with type 2 diabetes, moderate hypertriglyceridemia, and overweight or obesity (BMI 25-35 kg/m²) - will be enrolled through consecutive sampling and randomly assigned in a 1:1:1 ratio to one of three 12-week dietary interventions: a moderate low-carbohydrate, high-protein diet; a moderate low-carbohydrate, high-fat diet; or a standard diet consistent with usual clinical recommendations. No placebo is used, given the nature of the intervention.

The primary objective is to determine and compare changes in glycemic indices - HbA1c and fasting blood glucose - before and after the 12-week intervention, both within each of the three groups and between groups. Secondary objectives include comparing changes in lipid profile (triglycerides, total cholesterol, LDL-C, and HDL-C, with triglyceride reduction considered a key outcome of interest), anthropometric indices (body weight, BMI, and waist circumference), and systolic and diastolic blood pressure across the three groups. The study will also evaluate the level of dietary adherence in each group - measured through monthly self-reported adherence questionnaires and 24-hour dietary recalls - and examine how adherence relates to the observed changes in glycemic, lipid, and anthropometric measures. The incidence of diet-related side effects or adverse events will be compared across groups during the 12-week intervention and during a subsequent 30-day follow-up period.

Doses of participants' existing medications for diabetes, blood lipids, and blood pressure will be kept constant throughout the study wherever clinically safe to do so, in order to isolate and attribute observed changes to the dietary intervention itself rather than to changes in medication. Participants will be contacted monthly by phone for adherence support and safety monitoring, and will have blood samples (fasting glucose, HbA1c, and full lipid profile), body weight, waist circumference, and blood pressure measured at baseline and again at the end of the 12-week intervention, followed by one additional phone contact one month after the intervention ends to assess general well-being and any delayed adverse events (without repeat laboratory or anthropometric measurement at that final contact).

Applied objectives of the study include generating local, high-quality randomized-trial evidence to support individualized dietary choices (protein-focused versus fat-focused low-carbohydrate approaches) for Iranian patients with type 2 diabetes and hypertriglyceridemia, with attention to macronutrient quality (complex/fiber-rich carbohydrates, predominantly plant-based protein, unsaturated fats) consistent with the Iranian dietary pattern; assessing real-world dietary adherence and identifying barriers and facilitators relevant to clinical practice; and providing preliminary evidence that could inform future, longer-duration studies (6-12 months) examining potential reductions in medication requirements and the durability of metabolic improvements. Given the short 12-week intervention period, the trial is not designed to draw conclusions about long-term sustainability of effects.

Inclusion criteria

Diagnosed with type 2 diabetes mellitus for ≥6 months Fasting serum triglycerides between 200-399 mg/dL (based on the average of two measurements taken within a two-week period) Body mass index (BMI) between 25 and 35 kg/m² Age between 30 and 70 years If currently taking any medication for diabetes, dyslipidemia, or hypertension, the dose must have been stable for at least 8 weeks prior to enrollment, with confirmed adherence (having hypertension is not itself an inclusion requirement; only medication dose stability is required if such medication is being taken) Able to follow the prescribed diet Willing and able to provide informed consent

Exclusion criteria

Fasting triglycerides ≥400 mg/dL or <200 mg/dL HbA1c >10.5% eGFR <30 mL/min/1.73m² Type 1 diabetes or rare/uncommon metabolic disorders Severe renal, cardiac, or hepatic disease, or active pancreatitis Established cardiovascular disease (myocardial infarction, stroke, coronary angioplasty or bypass surgery, or heart failure) - controlled hypertension alone does not exclude Pregnancy, breastfeeding, or planning pregnancy during the study Psychiatric disorder or social circumstances that would prevent adherence to the dietary protocol Change in dose or type of diabetes, lipid-lowering, or blood-pressure medication within the 8 weeks before enrollment or during the study Use of weight-loss medications, protein supplements, or probiotics Body weight change >3% within the past 6 months (based on medical records or physician confirmation, not self-report alone) Withdrawal of consent to continue participation