The formation of type 2 diabetes is directly related to how our muscles convert sugar, a landmark new study has found.
Researchers at the University of Melbourne’s Medical School at the Austin Hospital have used elegant gene splicing technology to prove this popular theory about the biological cause of Type 2 diabetes.
This is the first strong evidence that when muscles fail to convert glucose into a substance called glycogen, it leads to the hallmarks of type 2 diabetes.
They hope the research will lead to development of a drug to that could convert glucose into glycogen when muscle metabolism fails.
- Muscle-specific gys1 knockdown in adult mice results in 70% reduction in skeletal muscle glycogen levels.
- Muscle-specific gys1 knockdown leads to glucose intolerance and peripheral insulin resistance.
- Muscle glycogen depletion caused impaired performance, as well as fatigue development during exercise.
Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity.
Molecular Metabolism – Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice
Chronic high glucose levels are associated with stroke, kidney failure, blindness and leg amputations. Most patients with diabetes die from heart attack or stroke. Yet researchers still know very little about the biological processes that lead to this condition.
Lead researcher on the project, University of Melbourne Associate Professor Sof Andrikopoulos, said the finding gives researchers a much better idea of where to target treatments for type 2 diabetes.
“We’ve known for decades the inability of muscle and fat to respond to insulin (known as insulin resistance) is a major mechanism that leads to high glucose levels in type 2 diabetes,” Assoc Prof Andrikopoulos said.
“If you have insulin resistance, the sugar stays in your bloodstream. So the inability of the muscle to transport sugar into the muscle cell is what leads to higher blood sugar levels.”
The researchers tested the theory with sophisticated gene technology. They effectively deleted the enzyme that makes glycogen from glucose from the muscle and watched what occurred.
“None of the drugs available at the moment treat the underlying cause of the disease.
“This provides us with more information about which pathways we should target to treat diabetes. Currently, we don’t have any drugs that target this pathway.
“The study also explains why one of the reasons patients with diabetes don’t exercise properly is that they may not have glycogen – if you improve your glycogen stores, you improve the ability to exercise.”
Diabetes is linked to cardiovascular disease, hypertension, stroke, mental illnesses and blindness. Currently, 1.7 million people live with diabetes. At the Austin, about one in three patients over 55 have diabetes.
SOURCES – University of Melbourne, Molecular Metabolism
In the past, postprandial hyperglycemia has been considered a risk factor associated mainly with diabetes. However, more recent evidence shows that it also presents an increased risk for atherosclerosis in the non-diabetic population and that high GI diets, high blood-sugar levels more generally, and diabetes are related to kidney disease as well.
Conversely, there are areas such as Peru and Asia where people eat high-glycemic index foods such as potatoes and high-GI rice without a high level of obesity or diabetes. The high consumption of legumes in South America and fresh fruit and vegetables in Asia likely lowers the glycemic effect in these individuals. The mixing of high- and low-GI carbohydrates produces moderate GI values.
A study from the University of Sydney in Australia suggests that having a breakfast of white bread and sugar-rich cereals, over time, may make a person susceptible to diabetes, heart disease, and even cancer.
A study published in the American Journal of Clinical Nutrition found that age-related adult macular degeneration (AMD), which leads to blindness, is 42% higher among people with a high-GI diet, and concluded that eating a lower-GI diet would eliminate 20% of AMD cases.
The American Diabetes Association supports glycemic index but warns that the total amount of carbohydrate in the food is still the strongest and most important indicator, and that everyone should make their own custom method that works best for them.
The International Life Sciences Institute concluded in 2011 that because there are many different ways of lowering glycemic response, not all of which have the same effects on health, “It is becoming evident that modifying the glycemic response of the diet should not be seen as a stand-alone strategy but rather as an element of an overall balanced diet and lifestyle.”
A systematic review of few human trials examined the potential of low GI diet to improve pregnancy outcomes. Potential benefits were still seen despite no ground breaking findings in maternal glycemia or pregnancy outcomes. In this regard, more women under low GI diet achieved the target treatment goal for the postprandial glycemic level and reduced their need for insulin treatment. A low GI diet may also provide greater benefits to overweight and obese women. Interestingly, intervention at an early stage of pregnancy has shown a tendency to lower birth weight and birth centile in infants born to women with GDM.
The number of grams of carbohydrate can have a bigger impact than glycemic index on blood sugar levels, depending on quantities. Consuming less dietary energy, losing weight, and carbohydrate counting can be better for lowering the blood sugar level. Carbohydrates impact glucose levels most profoundly, and two foods with the same carbohydrate content are, in general, comparable in their effects on blood sugar. A food with a low glycemic index may have a high carbohydrate content or vice versa; this can be accounted for with the glycemic load (GL). Consuming carbohydrates with a low glycemic index and calculating carbohydrate intake would produce the most stable blood sugar levels.
Criticism and alternatives
High variability in response to identical meals after monitoring week-long glucose levels in study of 800 people & 47,000 meals. Zeevi, Cell 163:1079 2015, PMID 26590418 The glycemic index does not take into account other factors besides glycemic response, such as insulin response, which is measured by the insulin index and can be more appropriate in representing the effects from some food contents other than carbohydrates. In particular, since it is based on the area under the curve of the glucose response over time from ingesting a subject food, the shape of the curve has no bearing on the corresponding GI value. The glucose response can rise to a high level and fall quickly, or rise less high but remain there for a longer time, and have the same area under the curve. For subjects with type 1 diabetes who do not have an insulin response, the rate of appearance of glucose after ingestion represents the absorption of the food itself. This glycemic response has been modeled, where the model parameters for the food enable prediction of the continuous effect of the food over time on glucose values, and not merely the ultimate effect that the GI represents.
Although the glycemic index provides some insights into the relative diabetic risk within specific food groups, it contains many counter-intuitive ratings. These include suggestions that bread generally has a higher glycemic ranking than sugar and that some potatoes are more glycemic than glucose. More significantly, studies such as that by Bazzano et al. demonstrate a significant beneficial diabetic effect for fruit compared to a substantial detrimental impact for fruit juice despite these having similar “low GI” ratings.
From blood glucose curves presented by Brand-Miller et al. the main distinguishing feature between average fruit and fruit juice blood glucose curves is the maximum slope of the leading edge of 4.38 mmol·L−1·h−1 for fruit and 6.71 mmol·L−1·h−1 for fruit juice. This raises the concept that the rate of increase in blood glucose may be a significant determinant particularly when comparing liquids to solids which release carbohydrates over time and therefore have an inherently greater area under the blood glucose curve.