Diabetes progresses on LC/HF Diet
The long-term effect of low-carbohydrate/high-fat diet on the development of diabetes mellitus in spontaneously diabetic rats
First the disclaimers:
- It's a rat study
- The OLETF rats used are a strain that become spontaneously diabetic and mildly obese -- however to the best of my knowledge this strain was not created by genetic manipulation (e.g. it's not a "knockout"). More here.
My excerpts will be from scattered around the article.
The long-term effect of low-carbohydrate/high-fat diets on the development of diabetes mellitus was studied in Otsuka Long-Evans Tokushima Fatty strain (OLETF) rats. Four groups of spontaneously diabetic (type 2) male rats at 10 weeks of age were pair-fed semi-purified powder diets containing different amounts of carbohydrate (80 %, 60 %, 40 %, 20 % of total calories) for 30 weeks. The carbohydrate content was isocalorically substituted for the fat content in the diet. At the onset of experimental feeding (10 weeks of age), an oral glucose tolerance test (OGTT) was normal in each group.
This was a fairly long term study for rats -- 40 weeks total. The first 10 weeks were simply to grow the rats. Although this is a spontaneously diabetic strain, the OGTT done at the start of the dietary intervention showed these rats were all still normal -- had not developed diabetes.
The rats were divided into four groups, diets contained the same calories, and although not mentioned, protein content was held constant as well. Only the carb/fat proportions were altered from LC (20%) to HC (80%) carbs in 20% increments with fat reduced proportionally. I'll call these LC (20%), MLC (40%), MHC (60%) and HC (80%)
Some background -- emphasis mine -- see text for citations.
Many epidemiological studies have already been performed to evaluate the relationship between dietary modification (low-carbohydrate/high-fat diet, LC/HF) and the development of DM. However, their results are contradictory. Some show negative associations, while others show positive associations. Even in animal experiments, some researchers studied the effect of high-fat feeding on the development of DM. However, the experimental duration of the test diet feeding was too short (less than 2 months) in most studies. Moreover, the experimental animals were allowed free access to the test diets in most of the studies. In general, diabetic animals select LC/HF as opposed to a high-carbohydrate/low-fat diet (HC/LF). In the previous studies, the animals consumed more LC/HF. Therefore, compared with the animals that were kept on the HC/LF, the calorie intake was higher in those fed LC/HF. From the results of the previous studies, it is difficult to draw any conclusion about the effect of LC/HF on the development of DM.
This is interesting that ad libitum, rats gain MORE weight on LC than LF because they eat more. This is counter to low carb dogma.
After 15 weeks of the test diet feeding there was no significant difference in the glucose tolerance among the 4 groups, although most of the rats were diabetic. The body weight increased with the decrease of the carbohydrate intake and increase of the fat intake (p < 0.05), and the difference increased in proportion to age (p < 0.05). The severity of diabetes mellitus was also increased along with the lower carbohydrate intake and higher fat intake, when the carbohydrate intake was less than 60 % (in energy).
So even with isocaloric intake, THESE rats gained MORE weight on low carb than high carb.
On the other hand, there was a significant increase in the 20 % group in the postload plasma insulin levels as compared with the other 3 groups at 40 weeks of age. Fasting plasma free fatty acid levels were increased in the lower carbohydrate content groups (20 % and 40 %) as compared with the higher carbohydrate content groups (60 % and 80 %) at the end of the experiment.
This is to be expected, and is so often ignored. Since these rats were only mildly obese, the elevated NEFA is probably an indication of some degree of insulin resistance in the fat cells.
Impairment of insulin secretion may be the cause of glucose intolerance induced by low carbohydrate intake rather than insulin resistance. These findings suggest that low-carbohydrate/high-fat diet aggravates diabetes mellitus in genetically diabetic rats, and that the development of diabetes mellitus is associated with the activation of the glucose-fatty acid cycle.
25 Weeks (15 Weeks Dietary Intervention)
40 Weeks = End of Study
The authors conclude that IGT is due to impaired insulin response (e.g. compromised beta cell function) and not skeletal muscle IR. I would have to question this because if you look at the tables above, we see that the LC group has a significantly higher insulin response to the glucose challenge at 30 min vs. all of the other groups. At 60 min, both the LC and MLC groups have higher insulin than the MHC and HC groups (insulin levels correlate inversely with carb), and at the 2 hour mark, only the LC group seems to have abnormally elevated insulin compared to the other groups. To me their results are consistent with IR -- in the fat tissue resulting in elevated NEFA, and peripherally resulting in the rats having to produce more insulin.
IF I'M READING THESE RESULTS INCORRECTLY, I WELCOME COMMENTS ON WHERE I'VE GONE WRONG.
Again, we have to remember this is a rat model, and one in which the males of this strain are predisposed to diabetes. However there is a strong genetic component to the development of T2 diabetes in humans. This study seems to indicate that while the LC'er may have better glycemic control, this is achieved at the expense of elevating the other circulating compound that results in dysfunction and damage -- NEFA's.
Bottom line: This study demonstrated that in genetically predisposed rats, diabetes developed and progressed further in those rats fed a LC diet than those fed a HC diet.