Pre-diabetes goes into remission on higher protein, lower carbohydrate diet


Can pre-diabetes be reversed with diet? This study says it can be

Type 2 diabetes currently affects 29.1 million people in the USA, 8 million do not know teh have it, they are currently undiagnosed.

Pre-diabetes affect 86 million Americans. This refers to having impaired glucose tolerance, which means glucose is not being cleared properly from the bloodstream and blood glucose remains higher than it should be. They do not yet have high enough blood glucose to warrant the diagnosis of diabetes.

Study protocol

  • Men and women between 20 and 50 whose BMI categorised them as obese (30 to 55 kg/m2)
  • All had prediabetes
  • They were randomly assigned to a high protein (18) or a high carbohydrate diet (20)
  • The study was for 6 months, 6 dropped out of HP group and 8 from HC group, 24 completed the study, 12 in each group
  • The HP diet was 30% kcals from protein, 40% kcals from CHO, 30% kcals from fat, versus HC diet; 15% kcals from protein, 55% kcals from CHO, 30% kcals from fat.
  • Subjects diet was calculated for each individual using resting metabolic rate (RMR) and 500 calories per day was subtracted in order to make it a calorically reduced diet to achieve weight loss.
  • Meals were pre-prepared and daily allowance was given as 3 meals and 2 snacks.
  • All subjects were not very active and stayed mainly inactive during the 6 months


  • Diets were designed so that all nutrients were covered, and they met all the recommended daily intake (RDI) goals for vitamins and minerals.
  • Dietary fat was primarily monounsaturated and polyunsaturated, plant oils, nuts and semi-liquid margarine.
  • Carbohydrate sources emphasized whole grains, fruits, vegetables and legumes; and dietary protein sources included lean meats, fish, chicken, eggs and non-fat dairy foods, that is, fat-free milk and low-fat cheese.


  • All meals were provided and food preferences catered for
  • Food records / diaries were kept and monitored


Done at the beginning and end (6 months) in order to determine changes in body weight and body composition (lean mass (LM) and fat mass (FM)), insulin sensitivity and glucose response, lipid profile, Ca metabolism and protein breakdown (by urinalysis).

Measurements taken:

  • Height and weight, blood pressure (BP) and waist measurements
  • OGTT and mixed meal tolerance test – Glucose and insulin were measured at baseline and at 30 min intervals for 2 hours
  • DXA scan, RMR, chemistry profile, complete blood count (CBC), vitamin D, parathyroid hormone (PTH) and lipid profiles
  • 24 hour urine collection tests were performed for creatinine clearance (CrCl), microalbumin, calcium (Ca) and urinary urea nitrogen (UUN).
  • Subjects were considered to have remission of their pre-diabetes if at 6 months they had a fasting glucose of <100 mg/dL, and a 2-hour glucose level of <140 mg/dL during a single OGTT.


Of great significance:

  • The 100% (12/12) remission of pre-diabetes to normal glucose tolerance in all the HP diet group subjects
  • There was only a 33% (4/12) remission in the HC group.
  • Subjects on the HP and HC had significant weight loss at 6 months from their Bl weights, however they were not significantly different between the HP and HC groups at 6 months.
  • HbA1c and insulin sensitivity (HOMA IR and ISI) were all significantly improved at 6 months from Bl in the HP and HC diets; however, the HP group had significantly greater improvement in these parameters compared with the HC group at 6 months.
  • However of more importance – The HP diet group’s percent lean body mass (LM) increased while percent body FM was decreased; whereas, the HC diet group lost both percent LM and FM. This preservation of percent LM in the HP diet group may be an important factor in improving insulin sensitivity since muscle is a major insulin sensitive tissue for glucose uptake. (Of note, neither group did any exercise over the 6 months)

The figure shows the effect of the HP and HC diets on percent changes in lean body mass and fat body mass at 6 months on the diets. HC, high carbohydrate; HP, high protein.
  • The HP group showed no bone loss or loss of Ca in the urine.
  • The cardiovascular factors (BP, cholesterol, triglycerides, LDL) and inflammation markers (TNFα, IL-6) were significantly decreased in both diet groups; the HP diet resulted in significantly greater reduction in the triglycerides, LDL, oxidative stress (ROS-DCF), TNFα, and IL-6 compared with the HC diet at 6 months. This reduction in TNFα, IL-6 demonstrates a better anti-inflammatory effect of the HP diet compared with the HC diet.

The figure shows the mean±SD of glucose and insulin for the 2-hour OGTTs and MTTs for the 12 HP diet subjects and the 12 HC diets subjects. The symbols represent the following: Embedded Image HP diet baseline (HP_Bl); Embedded Image HP diet at 6 months (HP_6 m); Embedded Image HC diet baseline (HC_Bl); and Embedded Image HC diet at 6 months (HC_6 m). p Values for the glucose AUC for the OGTTs are: HP_Bl versus HP_6 m=0.0005; HC_Bl versus HC_6 m=0.005; HP_6 m versus HC_6 m=0.0001. p Values for the insulin AUC for the OGTTs are: HP_Bl versus HP_6 m=0.0001; HC_Bl versus HC_6 m=0.005; HP_6 m versus HC_6 m=0.0001. p values for the glucose AUC for the MTTs are: HP_Bl versus HP_6 m=0.0005; HC_Bl versus HC_6 m=0.005; HP_Bl versus HC_Bl=0.01; HP_6 m versus HC_6 m=0.0001. p values for the insulin AUC for the MTTs are: HP_Bl versus HP_6 m=0.001; HC_Bl versus HC_6 m=0.01; HP_Bl versus HC_Bl=0.001; HP_6 m versus HC_6 m=0.0001. AUC, area under the curve; HC, high carbohydrate; HP, high protein; OGTT, oral glucose tolerance test.
  • Neither diet induced ketosis. Ketones were monitored by β-hydroxybutyrate determination on fasting blood during the study. β-Hydroxybutyrate for both groups showed no significant difference at 6 months from Bl and no significant difference between groups and demonstrated no significant ketosis induced by the diets.

My take:

  • This study was extremely well managed, food quality between the groups was the same, fat intake the same, however protein and carbohydrate differed.
  • Calories were reduced in both groups, however higher protein lower carb had significantly better results showing these macronutrients are critical when it comes to pre-diabetes.
  • Just losing weight did not have maximum impact on metabolic markers.
  • Increasing protein is critical to maintain lean mass. A 100kg person in this study was on around 1800 kcalories per day – assuming a 40% body fat, that is 60kg lean mass. 30% of 1800 means they were consuming 135g per day protein – that is approximately 2.2 grams per kg lean mass per day.  The 15% protein dieters were consuming just 1.1 gram per kg lean mass per day. Clearly inadequate to maintain lean mass.
  • Neither group had any measurable ketosis implying ketosis is not necessary for weight loss or reversal of pre-diabetes.
  • The difference in carbohydrates on an 1800 kcal day diet was 250grams on high carbohydrate and 180g on a lower carbohydrate diet. This amount was low enough to get the significant result.

Study link:

Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial


Objective Remission of pre-diabetes to normal is an important health concern which has had little success in the past. This study objective was to determine the effect on remission of pre-diabetes with a high protein (HP) versus high carbohydrate (HC) diet and effects on metabolic parameters, lean and fat body mass in prediabetic, obese subjects after 6 months of dietary intervention.

Research design and methods We recruited and randomized 24 pre-diabetes women and men to either a HP (30% protein, 30% fat, 40% carbohydrate; n=12) or HC (15% protein, 30% fat, 55% carbohydrate; n=12) diet feeding study for 6 months in this randomized controlled trial. All meals were provided to subjects for 6 months with daily food menus for HP or HC compliance with weekly food pick-up and weight measurements. At baseline and after 6 months on the respective diets oral glucose tolerance and meal tolerance tests were performed with glucose and insulin measurements and dual energy X-ray absorptiometry scans.

Results After 6 months on the HP diet, 100% of the subjects had remission of their pre-diabetes to normal glucose tolerance, whereas only 33.3% of subjects on the HC diet had remission of their pre-diabetes. The HP diet group exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), (5) increased percent lean body mass (p=0.001) compared with the HC diet at 6 months.

Conclusions This is the first dietary intervention feeding study, to the best of our knowledge, to report 100% remission of pre-diabetes with a HP diet and significant improvement in metabolic parameters and anti-inflammatory effects compared with a HC diet at 6 months.