The current treatment approach for type 2 diabetes is based on the blood glucose paradigm. Under this paradigm, most of the toxicity of T2D is due to the high blood sugar (hyperglycemia). Therefore, it follows that lowering blood glucose will ameliorate the complications even though we are not directly treating the T2D itself (high insulin resistance).
The ACCORD study was a test of this glucotoxicity paradigm, and unfortunately, it was essentially a failure. Patients were randomized to tight blood glucose control versus usual control, with the expectation that tight control would show tremendous benefits. Instead, the trial found none.
A total failure?
The mainstream media is picking up the fact that most of our current drug therapies for type 2 diabetes don’t seem to provide much of a real benefit (some exceptions are the newer class SGLT-2 inhibitors and GLP-1 agonists that have shown reduction in cardiac events).
The Canadian Broadcasting Company, for example, recently ran a headline that ‘New Study questions type 2 diabetes treatment – No evidence glucose lowering drugs help ward off complications“. Which makes sense. Drugs don’t cure a dietary disease.
Type 2 diabetes starts as a disease of insulin resistance and hyperinsulinemia. So why focus on lowering blood glucose, which is only the symptom? It is true that high blood sugars can cause problems, but lowering them with drugs does not treat the real problem- high insulin levels and insulin resistance.
The problem is one of perspective. As long as you believe that hyperglycaemia is the main cause of morbidity, you expect that lowering blood glucose will provide benefits. The ACCORD study proved this glucotoxicity paradigm is incomplete at best. Instead, the high blood glucose results from insulin resistance and hyperinsulinemia.
The root of the problem
Imagine it this way. Type 2 diabetes is essentially a disease of too much glucose in your body. Not just the blood, but the entire body. If you fill up the cells of your body with glucose, then pretty soon no more can be pushed into the cells, so glucose spills over into the blood. But the underlying problem is overflow. Insulin resistance is an overflow of glucose.
Using more insulin to move the toxic glucose from the blood into the cell accomplishes nothing. If you have too much glucose in the body, you can do two things – don’t put any more in, or burn it off. Simply moving the glucose around the body so you can’t see it is not useful. And that’s what most diabetes medications do.
Interestingly, the ACCORD study was not the first failure of the blood glucose paradigm. The UKDPS study was also unable to significantly reduce cardiovascular events or prevent deaths with intensive blood glucose lowering in type 2 diabetes. This was not even the first time that treatment increased death rates. The Veterans Affairs Diabetes Feasibility Trial also found an increase in death rates in the intensive group, but it was not statistically significant because of the small trial size. The earlier University Group Diabetes Program had also compared an intensive versus standard group. It too was unable to find any benefit to intensive treatment. One certain subgroup, using tolbutamide (a sulfonylurea medication that increases insulin) did have a higher death rate, though.
It would also start a parade of failures including the ADVANCE, VADT, ORIGIN, TECOS, ELIXA and SAVOR studies. It was not a single study that failed. There were multiple failures all over the world.
Glucotoxicity and insulin toxicity
The failure should have blown away the prevailing glucotoxiciy paradigm like Enola Gay’s kiss. Certainly, at very high blood sugars there is harm to the body. But at the moderate levels of blood sugar seen in controlled type 2 diabetes, there is no benefit to further lowering with medications such as insulin. So clearly, the damage to the body does not result from glucotoxicity alone. The problem is that insulin itself in high doses can be toxic.
All these trials used medications that don’t lower the insulin. Both insulin and sulphonylureas increase insulin levels. Metformin and DPP4 medications are neutral for insulin. TZDs like rosiglitazone do not increase insulin, but increase insulin action.
If the problem is both insulin toxicity and glucotoxicity, then increasing insulin toxicity to reduce glucotoxicity is not a winning strategy. And all the studies were there to prove it.
Tight blood glucose lowering has no benefits
By 2016, a meta-analysis of all studies proved conclusively the futility of the blood glucose paradigm. Whether you are looking at overall deaths, heart attacks, or strokes, tight blood glucose lowering had no meaningful benefits.
However, these failures were not enough to convince diabetic associations to embrace new treatment paradigms. They were set in their ‘glucose mindset’ and seemingly ignored the evidence to the contrary.
For example, the Canadian Diabetes Association in 2013 guidelines still continues to recommend a target A1C of 7%. Why? Haven’t we just proven that lowering A1C from 8.5% to 7% provides no benefit? Why would we give more medications for no benefit?
The CDA can’t very well say “We have no clue what you should do”, so they give guidelines that go directly AGAINST the available evidence. Kind of like a Bizarro world Evidence-Based Medicine.
Then they write “Glycemic targets should be individualized”. If there should not be a target, then say so. This is precisely what this paper describes. There is no evidence for benefit of tight glycemic control, yet 95% of diabetic guidelines recommend target blood glucose and tight control with medications.
This slide compares the effect of tight glucose control on the outcomes of most importance to clinical medicine – death, heart attacks, strokes and amputation. Virtually all studies show there is no benefit for any of these outcomes.
Statements published that recommend tight control have been slowly dropping since the ACCORD study. When study after study comes out to refute the hypothesis, you might suspect something is up. In 2006, most published statements still recommended tight control. By 2016, only 25% did. That is, the overwhelming majority of experts knew that tight blood glucose control was irrelevant. So, why do we still obsess over blood glucose numbers in T2D?
Unfortunately, it’s likely because diabetes specialists have not yet understood that this disease is about hyperinsulinemia more than hyperglycaemia. The drug companies, on the other hand, are all too happy to leave the status quo, which is extraordinarily profitable for them.
So how do you treat the high blood sugars AND the high insulin levels, at the same time? That requires two things: put fewer carbs into your body, and burn more off. Put most simply, it requires a low-carb diet and intermittent fasting.
The full guide
If you want to learn more about how to reverse your type 2 diabetes on low carb, or troubleshoot if you run into any problem, check out our full guide below. Alternatively choose the quick start guide with only the two most effective simple steps!
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