Introduction
The prevalence of type 2 diabetes in the USA has increased dramatically in the last decade. According to the Centers for Disease Control and Prevention (CDC) National Diabetes Statistics Report of 2014 there are currently 29.1 million people with diabetes, 21 million are diagnosed and 8.1 million undiagnosed. The prevalence of subjects with impaired glucose tolerance (IGT) or pre-diabetes is in excess of 86 million.1 The Diabetes Prevention Program (DPP)2 and ACTNOW3 studies showed that the rate of conversion for IGT to type 2 diabetes is 7–10% per year with no significant difference in ethnicity. The primary risk factor for type 2 diabetes is obesity as 90% are either overweight or obese. As body mass index (BMI) increases from 23 to >35 kg/m2, there is a 93-fold increase in type 2 diabetes. Obesity also increases the risk of heart disease, hypertension and other metabolic diseases.4 Lifestyle changes, including weight loss and exercise, reduces the risk of developing diabetes by 58%,2 whereas therapeutic intervention reduces the risk by 32% (metformin)2 and 72% (pioglitazone)3 in pre-diabetes subjects. Few studies have been carried out to show some remission of pre-diabetes (IGT) to normal glucose tolerance with diets and weight loss.5 ,6
Our previous feeding study (all food provided) comparing a high protein (HP) diet in normal glucose tolerant, obese, premenopausal women showed similar weight loss over the 6 months. However, subjects on the HP diet had a significant improvement in insulin sensitivity, and decrease in cardiovascular risk (CVR) factors, inflammatory markers, oxidative stress7 and increase in GLP -1, GIP and gastrin8 at 6 months compared with the HC diet subjects. Other diet studies have recommended various methods for weight loss9–19 some of which suggested advantages of low carbohydrate (CHO),15 ,16 higher fat17 or HP diets.18
Observations substantiate the validity of using a HP diet for weight loss. Suppression of hunger and inducement of satiety have been observed with the HP diet.8 ,13 ,20 The thermic effect of feeding also increases with protein primarily by the increase in protein synthesis.21 The low glycemic index (GI) of foods high in proteins has also been observed to be a factor in maintaining satiety. A high GI meal induces hyperglycemia which is followed a few hours later by the sensation of hypoglycemia and an earlier return of hunger.22 The diet composition can alter a number of other variables even though the weight loss may be the same with an isocaloric HP versus a high carbohydrate (HC) diet. The plasma lipids which are a major CVR factor can be effected by the macronutrient diet composition.23 ,24 For instance, a decrease in triglycerides was observed on a low CHO diet.23 Protein intake by itself induces insulin release; however, it is a much less potent secretagogue for insulin than is glucose in normal individuals.25 This suggests that HP diets may help preserve the β cells by increasing sensitivity and decreasing insulin load per meal.
Higher protein content in the diet may also help maintain lean body mass.20 Studies showed nitrogen balance remained positive after a hypocaloric HP diet but became significantly negative after a hypocaloric HC diet.26
Another important aspect of a HP diet is the anti-inflammatory effect and decreased glucose area under the curve (AUC) compared with a HC diet as was shown in our previous study.7 Other studies have demonstrated that hyperglycemia during glucose challenge or elevation of FFA27 leads to activation of leukocytes and reactive oxygen species (ROS). We have also shown that hyperglycemia in vivo and in vitro activates T cells, increases inflammatory cytokines, lipid peroxidation, and ROS.28 Studies also have shown that hyperglycemia in type 2 diabetes and obesity is associated with increased inflammatory markers.29
In this diet feeding study, we investigated the effects of a HP diet (30% kcals from protein, 40% kcals from CHO and 30% kcals from fat) versus a HC diet (15% kcals from protein, 55% kcals from CHO and 30% kcals from fat) for 6 months on obese women and men with pre-diabetes with restriction of 500 kcal intake/day (based on resting metabolic rate (RMR)) on remission of pre-diabetes to normal glucose tolerance, insulin sensitivity, weight loss, changes in lean and fat body mass, inflammatory markers and CVR factors.