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Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes

Objective: Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet.

Research design: Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used.

Methods: Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat.

Results: The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged.

Conclusions: Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed.

Full-text

Alex’s Notes: There are many ways to correct type-2 diabetes. Most revolve around dieting coupled with proper exercise, but let’s ignore the latter for a moment and focus on the former. Dieting can take many forms, with (arguably) two of the most common suggestions being short-term fasting and low-carbohydrate diets.  The study at hand aimed to compare the effectiveness of these two over the course of three days for improving hyperglycemia in diabetics.

The sample size was a very small seven male subjects – three of which were on metformin, three of which were on sulfonylurea, and one who was untreated. All the medications were stopped about 41 days prior to the interventions, however, in order to normalize HbA1c levels. The subjects averaged 60 years of age, and had an average BMI of 31 kg/m2.

The seven subjects all underwent two 3-day interventions separated by a 4-week washout period. I attempted to outline the study design in the table below.

 

Low-carbohydrate diet

Fasting

Pre Day 1

Standardized dinner (55% carbohydrate, 15% protein, and 30% fat), to be ingested at 6pm at home. This was based on 25 kcal/kg body weight.

Day 1

Admitted to a clinical research unit for 4 days. Baseline blood samples taken at 7am.Subjects received a standard breakfast, lunch and dinner at 8am, 12pm, and 6pm, respectively. Standard meals were composed of 55% carbohydrate, 15% protein, and 30% fat. Caloric distribution was: breakfast 32%, lunch 40%, dinner 28%. Blood samples were obtained every 15 min after each meal for the first hour, every 30 min for the second and third hour and hourly thereafter until 8am the next morning. 24-hour urine was collected.

Day 2

Subjects were provided with the carbohydrate-free meals at 8am, 12pm, & 6pm daily. The carbohydrate-free meals were composed of < 3% carbohydrate, 15% protein, 82% fat. The amount of food energy provided in the meals was based on 25–30 kcal/kg body weight.

Fasting. Ingestion of water was encouraged. Black coffee, tea without sugar or cream, and calorie-free beverages were allowed.

Day 3

Day 4

Washout

As we can see, the study was highly controlled. The participants were under nearly constant observation, activity was limited to quite diversions such as reading or watching TV, and all food intake was controlled for.

Glucose

Overnight fasting glucose concentrations relative to the day 1 standard diet were reduced by 36% in the fasting group and by 18% in the low-carb group, and these values were independent of fasting insulin and glucagon concentrations. Thus, eliminating carbohydrates from the diet can account for half the morning fasting glucose reductions. Moreover, the entire blood glucose concentrations over 24-hours were reduced by 49% via fasting and by 35% via low-carb when compared to the standard diet, suggesting that about 70% of the reduction is attributable to a lack of dietary carbohydrates.

When looking at acute responses, blood glucose levels increased after meals, as expected, reaching a maximum at 1.5 h after breakfast, at 1 h after lunch, and at 2 h after dinner, and small but distinct increases in glucose concentration were detected after the meals of the low-carbohydrate group as well, at essentially the same times noted for the standard meals.

Insulin

Morning fasting insulin levels did not significantly change during the interventions and were not significantly different between the different diets. Taken with the above, it is clear that insulin is dissociated from glucose concentrations. As expected, the insulin concentration did not change throughout the 24-hour day when the subjects were fasting, and the net increase in response to the low-carbohydrate diet was 28% that of the standard diet response. This is easily explained by the alternative fuels such as protein, which is known to stimulate an insulin response.

C-peptide, glucagon, body weight, & urine

The C-peptide response was similar to the insulin response, indicating a lack of significant insulin turnover. Fasting glucagon concentrations were similar regardless of diet, and were rather stable throughout the 24-hour day. Body weight decreased 213 lbs to 210 lbs following the calorie-sufficient, carbohydrate-free diet and from 212 lbs to 205 lbs after fasting. The urinary glucose excretion decreased from 26.5g on the standard diet to 0.26g and to 0.07g on the carbohydrate-free and fasting diets, respectively.

Bottom line

Notwithstanding the purely male, small sample size, the current study was extremely controlled for, and provided some interesting data comparing low-carbohydrate diets to fasting. Honestly, since fasting cannot be done indefinitely, this study supports the notion of utilizing a low-carbohydrate diet for managing type-2 diabetes. That said, I still have several questions that will hopefully be answered in future studies:

  • The fasting diet was in caloric deficit. How would the low-carb diet fair if it also had a deficit?
  • What about intermittent fasting?
  • What about intermittent fasting combined with low-carbohydrate dieting?
  • Alternate day fasting?
  • Adherence?
 
 

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