Please select the eligibility criteria that correspond to the clinical trial below.
Title: Low-Carbohydrate Dietary Pattern on Glycemic Outcomes Trial
Brief Summary: The proposed randomized controlled trial will test the effect of a low-carbohydrate diet on hemoglobin A1c among individuals with elevated hemoglobin A1c that are within the range of prediabetes or diabetes. Results may provide evidence about the role of carbohydrate restriction in individuals with or at high risk of type 2 diabetes.


Options:
A: Inclusion Criteria:

* Type 2 diabetes with HbA1c between 48 mmol/mol and 97 mmol/mol with or without metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors
* Overweight or obesity with BMI ≥ 25 kg/m2 and desired weight loss
* Non-smokers for \> 1 year
* Willingness to abstain from alcohol for 6 weeks
* Hemoglobin \> 7 mmol/L for men and \> 6 mmol/L for women
* Estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73 m2

Exclusion Criteria:

* Critical illness as evaluated by the principal investigator
* Systemic corticosteroid treatment, e.g. prednisolone
* Reported or journalized severe food allergy or intolerance
* Reported or journalized severe gut disease e.g. Crohn's disease, Coeliac disease etc.
* Reported or journalized alcohol dependence syndrome
* Injectable diabetes medication, including insulin and GLP-1 analogues
* Sulfonylureas (SUs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, unless discontinuation is possible, in which case a 2-month wash-out is mandatory
* Repeated fasting plasma glucose \> 13.3 mmol/L
* Urine albumin / creatinine ratio \> 300 mg/g
* Lactation, pregnancy or planning of pregnancy during the study
* Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the principal investigator
* Presently participating in other clinical trials
B: Inclusion Criteria:

* Diagnosis of type 2 diabetes
* HbA1c 7-10%
* BMI (kg/m2) \> 25 and \< 40 and weight \< 280 lb.
* Skill at and willingness to perform capillary blood glucose self-monitoring ---Insulin (changed to long-acting basal during run-in) or sulfonylurea treatment

Exclusion Criteria:

* Age \> 65
* Weight \>280 lb
* Health conditions that may interfere with study participation or for which the study interventions may be contraindicated. These include: kidney stones or kidney disease (creatinine \> 1.3 and 1.5 mg/dL for females and males, respectively; proteinuria \> 300 ug/g creatinine); liver or gall bladder disease; significant heart disease (myocardial infarction in the past six months, prior or current evidence of congestive heart failure, other evidence of left ventricular (LV) dysfunction) or other indices of active cardiac abnormalities, (angina, electrocardiogram evidence of ischemia or transmural myocardial infarction), significant anemia; and cancer (other than effectively treated non melanomatous skin cancer and surgically treated cervical cancer in situ).
* Current hypokalemia defined as serum potassium levels \<3.5 mg/dL.
* Osteoporosis
* Type 1 diabetes (history of ketoacidosis or undetectable fasting C-peptide levels)
* History of severe or repeated hypoglycemia, or hypoglycemia unawareness. Lack of recourse to another person in the immediate vicinity in the unlikely event that they require outside assistance for severe hypoglycemia.
* Triglyceride levels \> 400 mg/dL.
* Inability or unwillingness to comply with any aspects of the dietary and research protocol.
* Weight changes \> 10 lbs in the past three months.
* History of binge eating disorder or other eating disorders.
* Pregnancy or intention to become pregnant in the next 12 months.
* Current oral hypoglycemic medication that raises the blood insulin level
C: Inclusion Criteria:

* Men or women ages 40 to 70 years
* HbA1c 6.0-6.9%
* Willing and able to provide informed consent

Exclusion Criteria:

* Diagnosed type 1 diabetes mellitus
* Use of agents affecting glycemic control (medications for diabetes, oral glucocorticoids) within the past three months prior to enrollment
* Medical condition in which low-carbohydrate diet may not be advised: estimated glomerular filtration rate (eGFR) ≤45 mL/min/1.73 m²; self-report of liver disease due to hepatitis or alcohol; osteoporosis; untreated thyroid disease; gout; cancer (other than non-melanoma skin cancer) requiring treatment in the past year, unless prognosis is excellent
* Factors that may affect HbA1c: hemoglobin \<11 mg/dL (cutpoint for moderate-to-severe anemia, which could lead to falsely elevated or lowered HbA1c); recent blood donation or blood transfusion (self-report, past 4 months); human immunodeficiency virus (self-report)
* Self-reported history of intensive care unit stay due to Coronavirus Disease 2019 (COVID-19) in the past three months, as severe COVID-19 may affect blood glucose levels
* Allergies to nuts
* For women, current pregnancy, breastfeeding, or plans to become pregnant during the study
* Consumption of ≥21 alcoholic drinks per week or consumption of ≥6 drinks per occasion
* Current or planned residence making it difficult to meet trial requirements (due to distance from study site and/or challenges regularly traveling to site)
* Current participation in another lifestyle intervention trial or a pharmaceutical trial
* Participation of another household member in the study; employees or persons living with employees of the study
* Other concerns regarding ability to meet trial requirements, at the discretion of the principal investigator or study coordinator
D: Inclusion Criteria:

* physician-diagnosed T2D of ≥1 year;
* current HbA1c of \< 8.5%;
* BMI: \>25 kg/m2; (as of July 5, 2021, BMI cut off was expanded from 25-40 kg/m2 to higher than 25kg/m2 to facilitate recruitment)
* blood pressure of \<160/99 mm Hg assessed according to guidelines;
* non-smoking;
* not on hormone replacement therapy, corticosteroids, or anti-inflammatory medications;
* 20-79 years old.

Exclusion Criteria:

* Use of exogenous insulin;
* taking more than 2 glucose lowering medications;
* ongoing medical treatment for diseases such as cancer, auto-immune or inflammatory disease, liver or kidney disorders;
* allergy, intolerance or aversion to eggs or any other dietary restrictions (e.g., vegan, breakfast skipping) that will prevent them from following the standardized study diets;
* being unable to follow remote guidance by internet or smartphone
* being unable to follow the controlled diet instructions;.

Answer: C