Joseph Kraft: Why hyperinsulinemia matters
Dr Joseph Kraft MD, pathologist and author of “Diabetes Epidemic and You” and unsung pioneer in insulin responses and early diagnosis of diabetes
Science has a history of ignoring some of the most important and astonishing work for a long time, then coming to its senses and celebrating it. It is time now to celebrate the work of Dr Joseph Kraft MD, a pathologist now in his nineties. Dr Kraft is the author of “Diabetes Epidemic and You” which is still available, at least in hard copy. He defines what he calls “Diabetes in situ” which is borrowed from his cancer pathology background. He has written several good papers, none of which have ended up being cited that highly. A nice, free summary of his work is available here. Kraft has carried out more than 14,000 oral glucose tolerance tests over a few decades. Normally we measure the glucose response to drinking glucose. This response can tell us the degree to which we metabolize and remove glucose from our blood. Very important for diabetes diagnosis and other metabolic issues. Kraft’s test are different though. He is way more thorough than normal. First, rather than monitoring glucose for 2 hours post test, he monitors it for at least 5 hours. Second, he also measures insulin, as well as glucose, over the course of the test. From his test results and the other literature, as well as his pathology and direct autopsy observations, he concludes that:
- We may be able to diagnose diabetes much much earlier than we do
- Abnormal insulin levels (high) are directly and indirectly damaging to the vascular system, and therefore almost every organ in the body
- This high insulin (hyperinsulinemia) is a condition in its own right and really the causal mechanism behind most of the metabolic and chronic diseases we experience today.
He calls the abnormal insulin response, with normal glucose response “Diabetes In Situ” What is Diabetes In Situ? Here’s the deal – you go to your doctor. You get a series of tests to see how well you are functioning metabolically. This is a really important series of tests because metabolic functioning is what will determine almost all of our quantity and quality of life. I would go as far as to at least hypothesize (there’s enough evidence) that problems in carbohydrate metabolism are implicated in virtually every chronic disease from head to foot, and most of the organs in between. This includes Alzheimer’s and vascular dementia, peripheral vascular disease and everything in between, from common obesity to diabetes to fatty liver disease to cardiovascular disease…and the list goes on. The trouble is that your doctor will look for metabolic markers which are either flawed as predictors, or mostly are markers of end stage dysfunction. Things like elevated blood glucose, high blood pressure, vascular blockages (arterial sclerosis) etc. If your doctor is really interested in your health and suspects you aren’t doing that well, they might order an oral glucose tolerance test. Kraft shows us that there are five typical patterns of insulin response to the glucose which characterize disease state. As mentioned earlier, these are really what we should be considering in early identification of metabolic problems. Unfortunately, the glucose tolerance test is rarely run long enough, nor is insulin (key to this) measured concurrently. In fact, in New Zealand, insulin measurement can only be ordered and covered under the public hospital system by a handful of specialist endocrinologists. Insulin is not considered as useful in the diagnosis of early stage chronic disease. That’s a shame really because Dr Kraft shows it certainly is useful. Let’s look at Kraft’s five patterns….. Here’s what we consider a normal insulin response to a glucose bolus in an oral glucose tolerance test. Kraft calls this “Pattern 1”. Pattern 1 insulin peaks after a 75 or 100 g glucose load after 30 to 60 min at 50-70 units. Everything is almost back to baseline after 2 hours, certainly after 3 hours. This is what we regard as a normal insulin response to a glucose load. It’s also likely that slower release carbs (lower GI) like beans might provoke an even lower area under the curve for the same total CHO load. 
Pattern 2 (below) is the first sign of insulin resistance, but things will likely look fine if you simply look at the glucose responses. We see a similar time to peak, but a much higher peak. Insulin hasn’t returned to close to baseline until 4 hours or so after the initial load. The area under the insulin curve is very large. The total stress on pancreatic beta cells is high simply because of the overall demand for insulin. Many (most) people with this pattern present normal glucose curves and are told they are doing “just fine”.
Pattern 3 (below) is a delayed and high peak. This is indicative of some beta cell function, but some functional loss. In essence we are seeing the beginning of beta cell burn out. People can eventually move glucose into their cells, but they take a long time to produce enough insulin.
Pattern 4 (below) is the same as Pattern 3 except the fasting level of insulin is much higher.
Pattern 5 (below) is beta cell failure. In other words, there is little or no ability to move the glucose into cells because the pancreas can’t produce insulin. Patients will need exogenous insulin injected at that point to get the same result. Interestingly, Kraft also shows that sometimes people on low carb diets can show this pattern temporarily. It’s not that they are unable to produce insulin, it’s just more likely that they can take up glucose into cells (eg, brain) without insulin in the first instance. These people return to Pattern 1 after a period on a higher carb diet. I think this is also consistent with the finding that people on LCHF diets typically have a temporary diagnosis of peripheral insulin resistance which is resolved after a large carb meal. It’s likely that the body adapts to preferentially shunt the available glucose to the brain first. So Pattern 5 with a low carb diet is OK, its jus the same physiology as Pattern 1 but adapted to low carb. 
Take-home messages, implications for practice, and questions
- Dr Kraft was onto it decades ago – that we should measure glucose and insulin concurrently for an extended period in the glucose tolerance test to identify those people who are at risk early.
- This early detection is both ethical and necessary.
- Instead current best practice sends people away who are insulin resistant until they present with end stage disease markers. Only then will we take them seriously.
- Why haven’t we taken Dr Kraft’s excellent work more seriously?
Finally here is a link to a letter I received from Dr Kraft recently. He outlines is overall approach and ideas from his results of several thousand OGTTs over several decades. It’s interesting stuff – page 1 click here – page 2 click here
As usual, for all my blog thanks so much to Helen Kilding who tirelessly edits and corrects my terrible typing!
The Science of Human Potential 
Some thoughts – the liver is the insulin clearance organ and high insulin with normal glucose clearance could be a sign of poor liver function. The so-called liver function tests are actually liver damage and inflammation tests, and may not detect a fatty liver that is not inflamed.
“NAFLD is present in approximately 80% of
patients with T2D, and T2D is present in 21–45% of patients with
NAFLD, with glucose intolerance present in up to 70% if an oral
glucose tolerance test (OGTT) is performed.”
http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2009.06164.x/pdf
But what about the other 30%, and what about those who have not attained the threshold for NAFLD diagnosis?
“A limitation of these studies is that subjects with NAFLD and
normal liver enzymes were not included in the case population.4–6
Liver enzyme changes are neither highly sensitive nor specific to
accumulation of fat in the liver and related liver damage. Further,
only a minority of patients with T2D have abnormal liver enzymes,
while the entire histological spectrum of NAFLD can be seen in
patients with normal liver enzymes.7,8 Thus, normal liver enzymes
is not a perfect criterion to exclude NAFLD, and patients with
alterations in glucose metabolism and insulin resistance despite
normal ALT should also be considered in selecting cases of possible NAFLD for hepatic imaging and/or histological assessment.8”
What causes NAFLD? I have no doubt that this is due to high intake of linoleic acid and sugars in most cases, sometimes compounded by choline deficiency. This is what produces the syndrome in animals, and it resembles the fast food/convenience food/poverty food diet associated with NAFLD – and DM2 – today.
P.S. I liked this bit in the Kraft paper
“Demonstration that alteration of
carbohydrate intake could affect insulin
response has been used to monitor
effectiveness of diet in diabetic
management programs. Figs. 8B, 9A and
9B are examples taken from patients
with diabetes mellitus in situ who were
placed on low carbohydrate diets and reevaluated after one year. All changed to
an entirely normal pattern and only in
one instance was there appreciable
weight reduction [5kg (11lb.)]. The fact
that diet alters insulin pattern was further
supported by the case illustrated in Fig.
10A in which a low carbohydrate diet
was followed by a typical low insulin
response. “
Yes it’s good stuff and it happened with weight stability
I started having the spikes and drops in blood sugar/insulin (hyper/hypoglycemia) in my 20s and was given a glucose tolerance test which was analyzed to indicate my symptoms were not correlated with my glucose levels. I have long suspected that my symptoms were correlated to my insulin levels, which were not tested. At that time, I was dismissed as having “crock” symptoms (meaning that they were psychological) despite my major family history of Type II Diabetes. If Kraft had been taken seriously years ago and my insulin levels had been concurrently measured, then I might have taken dietary measures earlier and avoided years of misery and not have accelerated progressive insulin resistance.
I asked my endo once if i could get my glucose and insulin tested together and he said it would be a waste of time, won’t show anything signficant. I am trying to follow a lower carb diet myself and finding it kind of hard to stick too after about a month, supplements of vitad3 and gtf and cinnomon may just help me to be able to stick to it better. right now suffering rather badly from the change, is it possible to get sick when you reduce your sugar intake, increase fruit and veggie intakes nad reduce flour products say about 80 percent?like nausea, headaches, the runs, fatigue and lightheaededness and some weakness?is that a withdraw of adrenalin and cortisol you get when you overconsume bad carbs alot and adrenalin helps overcome the inuslin resistance caused by the hyperinsulinemia response (cellular resistance). you know your body was counteracting the high adrenalin alot and you don’t have it so it has to recalibrate itself again? any thoughts on this? thanks.
Hi Grant, a couple of questions for you.
1. what does this say about the vakue of fasting blood glucose levels?
2. is the blood glucose normal range too high, perhaps because it was established from a group of possibly (or probably) abnormal individuals; as was probably true for cholesterol normal ranges.
1. What does this say about the value of fasting blood glucose levels?
In my opinion, fasting blood glucose levels are very useful to monitor pancreatic decompensation. Hyperglycaemia is a big risk to long-term health. But there has been 8-10 years worth of pancreatic damage before getting to the stage when blood glucose starts rising.
[Zavaroni, I., Bonini, L., Gasparini, P., Barilli, A., Zuccarelli, A., Dall’Aglio, E., . . . Reaven, G. (1999). Hyperinsulinemia in a normal population as a predictor of non—insulin-dependent diabetes mellitus, hypertension, and coronary heart disease: The Barilla factory revisited.]
2. is the blood glucose normal range too high, perhaps because it was established from a group of possibly (or probably) abnormal individuals; as was probably true for cholesterol normal ranges.
The blood glucose levels to define diabetes, impaired fasting glucose and impaired glucose tolerance, as set by the WHO in 1999, were revised in 2006 and the levels were lowered at that point. The WHO states in its report “In the absence of a more specific biological marker to define diabetes, plasma glucose estimation remains the basis of diagnostic criteria” (p.g. 9). Based on current literature, these glucose levels do help to predict increased risk of diabetes complications, without over-burdening the health system.
[http://www.who.int/diabetes/publications/diagnosis_diabetes2006/en/index.html]
I personally believe though that the time has come to re-evaluate insulin as a more specific diagnostic marker. One reason why organisations may not choose to do this is that many more people will be diagnosed with diabetes placing great burden on an already burdened health system, but the results will pay off in the longer term with a healthier population.
Hi Grant,
Does Dr. Kraft have a pathological process in mind for the vascular damage associated with hyperinsulinaemia? Perhaps I am being stupid (I’m on a nightshift!) but I always thought it was the reactivity of glucose/fructose doing the harm; what he is saying is that even with normal FBG the disease process can have started. So what is causing the endothelial damage?
Yes I think he evidence is there or a direct inflammatory effect as well as the IGF pathway
Forgot about IGF.
How do you feel about deliberate use of insulin spikes on a weekly basis for anabolic reasons…?! It works. But I’m trying to weigh up how much I’m risking my future health! (Low carb the remaining week).
Thank you for directing me to this information.
I’ve read Dr Kraft’s book now and I’m trying to find an
endocrinologist/testing center where I can get
a 5 hour glucose 100g test with insulin assay.
Might be a difficult endeavor.
He doesn’t say too much about what treatment to take once
occult diabetes is found. I’ve been on an LCHF
diet for over 2 years.
Over the past 10 years
I have been afflicted with most of the illnesses
related to T2DM he cites in his book and never
in my diagnosis/course of treatments did a doctor suggest
that I might have T2DM.
Thanks again.
The good news is that you can work out your “Kraft pattern” with a 3-hour oral glucose tolerance test with insulin assay using time to peak and 2+3 hour sum (rather than 5-hours). I’m not sure where you are based but this can only be done privately in New Zealand. When you get to go ahead with your test, Dr Kraft recommended “two or more weeks” of standard high carbohydrate diet to ensure that you achieve true response pattern, rather than a “low-insulin response”. Now it looks like they recommend carbohydrate 200g/day for three days before the test.
As Dr Kraft is a pathologist, treating patients was not his clinical area, but staying LCHF is a good idea, but you may need to enter nutritional ketosis to get the best benefit. Ensuring you have plenty of physical activity will also improve insulin sensitivity.
The paper that Grant cites does discuss patients with abnormal Kraft patterns being restored to a normal pattern after a year of a carbohydrate restricted diet.
I am 58 and have been diabetic since I was 40 and put on insulin around 6 years later, but had unstable blood sugar issues at least since I was in my 20s. I have slowly become more and more insulin resistant.
I struggled for years with fungal and Candida issues which was only addressed after following a very low carb healing diet for several years, plus dumping gluten. Years of IBS stopped within hours of dumping gluten as did more gradually the restless leg syndrome, ‘diabetic’ neuropathy burning feet & painful toes), GERD, palpitations, hiatus hernia, night sweats, hot flushes, gastroparesis, and age/liver spots, etc.
However, I still have worms. Sadly the diet did not address them. Neither has my doctor. And no, I am neither delusional, suffering from Formication nor a psychiatric nutcase…..
Judging by the historical symptoms that I now know to be connected to worm activity in my body, they and their subsequent offspring have been there since I was a child. I am convinced they are somehow behind the diabetes.
Interestingly, there was a study done recently finding that dragonflies that are infested with a particular parasite develop metabolic syndrome. The authors hypothesized whether diabetes/metabolic syndrome in humans could also be triggered by parasites/microbes. As de-worming of humans living in ‘Western’ society sailed out of the window some 50-60 years ago, as diabetes began its exponential climb, I would suggest that to be a very valid hypothesis…….
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My son had a 5hour ogtt and levels were:fasting 88, 71, 75, 69, 69, 76. His symptoms are headaches, lethargy, loss of color in face. What does the drop after baseline indicate? Thank you.