Sugar and Diabetes

Introduction

It seems as if many theories about nutrition take hold in popular culture as a function of our human tendency towards word association.

The old belief, held by many even today, that eating fat will lead a person to become fat is probably partly rooted in the words we use. However this belief is somewhat misguided (calories are the main dietary determinant of weight loss, not fat), so why did it catch on? Well, would so many people have clung fervently to the idea that a low-fat diet should be the go to for weight loss had we called the fat on our bodies “adipose tissue” as it is so often referred to in the medical field? What if we called the fat in our diet “lipids”, or some other interchangeable term? In an alternate universe following a different lexicon would there have been as many people following a low-lipid diet for the purpose of adipose tissue reduction?

Phrased like that I kind of doubt it.

A similar example can probably be noted in the widespread idea that sugar causes diabetes. Diabetes is a disease characterized by high blood sugar. Even though the sugar in this scenario is in fact glucose, the use of the word “sugar” has almost certainly established in the minds of people a connection between this “sugar” in the blood and your basic dietary sugar, made up of glucose and fructose.

Were our colloquialisms more accurate we would say diabetics have high blood glucose and call “sugar” either sucrose or a mixture of glucose and fructose, whichever was more appropriate in the situation. This may have alleviated some of the unscientific condemnation of “sugar” as a cause of diabetes and the inevitable recommendation that diabetics avoid sugar at all costs.

Clearly I am beginning this post with some critical pronouncements. However, this issue is, in my opinion, one of the most complex, misunderstood, and important topics in nutrition today. The vilification of fructose is an increasingly popular dogma which I strongly oppose not just because I disagree with it, but because of the ramifications of this belief. Some health “professionals” have gone so far as to make the obstructive claim that fruit is contraindicated in people with diabetes and a risky food in general given the fructose it contains.

Bullshit.

In this post I will be evaluating the belief that “sugar causes diabetes” primarily by critically evaluating the claim that fructose adversely affects insulin sensitivity.

You may be aware of evidence that supporting insulin sensitivity and avoiding insulin resistance is fairly important, both for avoiding diabetes and possibly for the prevention of some other serious diseases (I.E. cancer). So if fructose causes insulin resistance it would seems valuable to avoid it.

As you will perhaps be surprised to learn given my opinionated introduction there are situations in which I believe fructose can adversely affect insulin sensitivity, but these are probably few and far between and, more importantly, the demonization of fructose is an oversimplification which causes us to ignore more important elements of our diet.

The Effects of Fructose on Diabetics

I think one interesting perspective on this issues comes from looking at the effect fructose on diabetics, particularly type 2 diabetics, as folks with this condition have a pathological (abnormal, illness causing) level of insulin resistance and dysfunctional glucose control. I mean, If we want to know if fructose causes diabetes, why not see how it affects people with diabetes?

Interestingly enough, the evidence is essentially universal that fructose, compared to either glucose or starch, does not worsen existing diabetes.

Several small studies on diabetics, lasting between 4 weeks and 3 months, have shown no effect of fructose on markers of insulin resistance (1-8), even when as much as 110 grams of fructose were consumed in place of nearly none (6,7).

A much longer controlled study on fructose and diabetics lasted an entire year (9). It reported that the addition of 20 to 30 grams grams of fructose to the diet of 20 diabetics (types 1 and 2) had no effect on indicators of insulin sensitivity. However, this study included only 6 total type 2 diabetics

If you’re not impressed or satisfied by these studies, a number of similar studies have reported fructose was helpful for diabetics.

In a crossover study at a Minnesota hospital, 12 diabetics were fed 21-23% of their dietary calories as either fructose, sucrose, or starch (10). After 8 days those on the fructose diet had lower one and two hour post meal glucose levels, lower overall blood glucose levels, and less urinary glucose excretion in both the type 1 and type 2 diabetics. A 28 day study on 18 diabetics by the same researchers who performed the previous study (including diabetes researcher John Bantle) found that obtaining 20% of calories from fructose compared to starch led to a 12.5% decrease in plasma glucose levels, a decrease in glycated albumin in the T1 diabetics, and a decrease in urinary glucose (11). Glucose levels throughout the day also tended to be lower in the fructose group, a common finding.

In a 4 week study on ten type 2 diabetics the effect of about 45-65 grams of fructose or a placebo (glucose based) were tested (12). At the end of the trail the fructose group saw a decrease in HbA1c and improved insulin sensitivity (a not-to-shabby 34 percent increase), while the control group saw no difference on these parameters.

A similar study, also lasting 4 weeks, also on ten T2 diabetics (non-insulin dependent) found that replacing 25% of dietary carbohydrates with fructose led to lower blood glucose levels during an oral glucose tolerance test (13).

In a 9 week study on ambulatory type 2 diabetics, 60 grams of crystalline fructose was added to the diet of one group and was not added to the diet of the other group (14). By the end of the trail the 9 diabetics given fructose experienced a significant decrease in fasting blood glucose and glycated hemoglobin, while the other group saw these values increase non-significantly.

Yet another study on 14 diabetic men found that adding 50-60 grams of fructose to their diet for 24 weeks, a week of which was in a hospital setting, frequently brought about lower fasting plasma glucose levels (15).

A 3 month study examined the effect of adding small amounts (about 23 grams) of either fructose or starch to the diet of 26 type 2 diabetics (16). The addition of fructose had no negative effects, even lowering levels of fructosamine and glycated hemoglobin compared to the addition starch.

Finally, one of the longest studies of the bunch was another crossover study in which 13 poorly controlled type 2 diabetics either consumed 60 grams of fructose (contributing 15% of their total calories) or didn’t for 6 months, at which time everyone switched groups (17). After half a year following the diet, the diabetics with the added fructose saw heir serum glucose and glycosylated hemoglobin decrease significantly while the control diet saw both of these values increase non-significantly. No negative effects of fructose on serum lipids were observed.

When considering all the available evidence, as has been done in some meta analysis (18), fructose appears to improve insulin sensitivity in diabetics as indicated by a decrease in levels blood glucose and glycated proteins. Clearly, fructose shouldn’t be of large concern to most diabetics.

However, this doesn’t mean fructose doesn’t worsen insulin sensitivity in everyone else. It would be a leap in judgement to assume the cause can’t sometimes be the cure. With that in mind let us proceed!

Fructose Worsens Insulin Sensitivity In Large Quantities

A number of studies have shown negative effects of fructose on insulin sensitivity in non-diabetics as assed by a variety of methods. However, as we will soon see the amount of fructose needed to produce such effects is fairly large.

Perhaps the first major trial suggesting an adverse effect of sugar on insulin sensitivity was carried out in Israel in 1966 (19). In the study the majority of carbohydrates in the diet (about 300 grams per day) were supplied by either sugar or bread for 5 weeks. This study reported lesser insulin sensitivity in the high sucrose diet (and a higher fat “Western” diet) compared to the bread diet as assed by an oral glucose tolerance test:

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This study will prove to be one of several where a high fructose intake (in this case about 150 grams from about 300 grams of sucrose) negatively affected insulin sensitivity.

So while this study supports the notion that large amounts of fructose negatively affect insulin sensitivity it is a bit dated. The researchers didn’t measure serum insulin levels and thus this study should be considered weak evidence of sugars effect on insulin sensitivity, although we won’t be ignoring it completely.

More than a decade later a scientist named Sheldon Reiser performed a study on sugar in which 19 men and women were given diets varying only in the quantities of starch and sucrose contained therein (20). One diet contained roughly 227 grams of sucrose (or about 113 grams of fructose) while the other diet contained an equal amount of starch from wheat. Each diet was followed for about 6 weeks.

This time insulin was measured so a better picture of insulin sensitivity could be obtained.

The findings from this study suggests there was a decrease in insulin sensitivity in the sugar group. Fasting levels insulin and glucose were both higher in this group (graphs below) as were levels of insulin and glucose in response to an oral sucrose tolerance test.

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This study is decent evidence of an adverse effect of fructose on insulin sensitivity at a dose of 113 grams per day.

At this point we should jump in our nutrition time machine and move ahead 30 years to a decade which seemingly kicked off a wave of studies on fructose and insulin sensitivity. 2009 brought us a week long study on 16 healthy men in Switzerland (21). In this study the addition of 200 grams of fructose on top of the usual diets led to decreased insulin sensitivity in the liver but no such decreased insulin sensitivity of the entire body.

However, let’s be clear: there was no control group, this was just a study where a bunch of young guys ate 800 extra calories which just happened to be from fructose in addition to everything else they were eating and their livers became less insulin sensitive. Frankly, the fact that whole body insulin sensitivity wasn’t decreased should be the real news here. Luc Trappy, the lead researcher from this study, decided to repeat this experiment with a control group made to consume 200 grams of glucose while another group again consumed 200 grams of fructose (22). Both groups experienced similar decreases of their insulin sensitivity, suggesting that binging on empty calories was the main villain here. Another study by Luc Trappy a few years earlier also reported no negative effect of 200+ grams of fructose for one week on direct measures of insulin sensitivity, including a glycemic clamp, one of the better measures of insulin sensitivity (23). However, these studies were only a week long. It would be preferable to find studies lasting significantly longer.

2009 was also the year one of the most widely cited anti-fructose studies was published. In this study about 30 middle aged, overweight or obese men and women were given 25% or their calories as either fructose or glucose in the form of a tasty sweetened beverage (24). By the end of this 10 week study the subjects consuming the fructose has worse insulin sensitivity than the glucose group as assessed by a variety of methods, including an oral glucose tolerance test, fasting glucose and insulin levels, and other complex markers of insulin sensitivity.

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This study is perhaps rightfully one of the best studies suggesting large amounts of fructose worsen insulin sensitivity. Again, large amounts of fructose. In this case, 25% of calories, which would be someone’s fructose intake if half of all their calories came from sugar. The folks in this study were eating around 130 and 180 grams of fructose a day depending on their gender and calorie intake. Go eat a half a pound of white sugar every day for the next 10 weeks and you still have consumed less fructose than these folks.

Just to put in things in perspective.

Kaspar Berneis is a Swiss doctor who performs studies in the city of Zurich. He has published research (25) suggesting a 3 week fructose intake of 110 grams per day (HF) worsens insulin sensitivity as assessed by hepatic glucose output, but that no such negative effect occurs when a fructose intake of about 77 grams (MF) or 72 grams (HS) is compared to a fructose intake of about 40 grams (HG):

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However, hepatic glucose output may not be the best stand alone measure of insulin sensitivity so let’s look at another study performed by Dr. Kaspar Berneis.

In 2011 Berneis performed a study which is considered by some to be good evidence that even a moderate fructose intake can harmful (26). However, with respect to the effect of fructose on insulin sensitivity it truly shows no such thing. This study had not two, not three, not four, not even five, but a grand total of six different dietary groups (and they can all be yours for just $19.99, you just pay shipping and handling). Each group differed by the amount of fructose the subjects were consuming. Depending on the group subjects were taking in either 34, 47, 49, 79, 85, or 116 grams of fructose per day for 3 weeks, give or take a tablespoon or two.

Using data from the study an assessment of each groups insulin resistance (the opposite of insulin sensitivity) was calculated using what’s called a HOMA^2 IR. Although this data showed the highest fructose intake increased insulin resistance, no damning trend was found when this highest group was removed. Using the researchers data I have plotted insulin resistance levels of each group by their letter abbreviation with their fructose intake in parenthesis:

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As can be seen above a fructose intake of 116 grams per day did have negative effects but such insulin desensitizing effects were not observed when lower amounts were consumed.

Given the available evidence in this section, a fructose intake of 110 grams per day or higher does seem to worsen insulin sensitivity in non-diabetics. But is a lower intake really fine and dandy? Or is the evidence simply not conclusive for lower intakes? I’ll address this in the next section.

Are Moderate Amounts of Fructose Safe?

In this section I want to explore whether low doses of fructose are safe in non-diabetics and, if they are, around what dose does fructose start having negative effects. To achieve this I thought it would best to look at the effect of increasing doses of fructose, starting with the lowest dose studies and moving, for the most part, ever upwards.

In 1979 a study was published which examined the effect of fructose compared to dextrose (basically a form of starch) (27). Six subjects with high triglycerides in a University of Washington hospital were given a diet of either dextrose or dextrose and fructose, sometimes with added fat from butter and corn oil. Oh and dried milk for protein. Yummy! When the diet contained fat the fructose intake was 33 to 46 grams in the fructose containing diet versus none in the dextrose only diet. When the diet contained zero fat the fructose intake was 90 to 154 grams versus, again, none. Neither intake of fructose, either the lower or higher amount, caused levels of glucose or insulin to rise. However, no glucose tolerance test was performed and this study contained only a few people eating a highly refined hospital diet, so these results may not be the best evidence of much.

A recent study on 28 subjects with chronic kidney disease looked at the effects of 60 or 12 grams of fructose in the daily diet for 6 weeks (28). Insulin resistance as assessed by fasting glucose levels and HOMA showed no apparent affect of the higher fructose diet on insulin resistance. However, while this study was well designed it utilized subjects with kidney disease and thus may not be applicable to the general population.

When 24 healthy men and women were randomized to a diet with either 85 or 15 grams of fructose no difference in fasting or daily levels of blood glucose or insulin after 42 days between the two diets (31). Daily blood glucose and insulin levels even tended to be lower on the higher fructose diet:

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However, once again this study used indirect markers of insulin sensitivity and should thus be taken as weak evidence of the safety of fructose.

Scandinavian researchers compared the effects of 75 to 80 grams of fructose with an equal amount of sucrose or starch for 10 to 20 days and noted no negative effects of fructose on glycated red blood cells, a crude marker of blood glucose levels in the blood over time (30). Let’s not put much weight on this study.

11 healthy adults were placed on a 14 day diet in which they ate 63 to 99 grams of fructose (in place of a similar amount of sucrose) (32). After an initial adaptation period there was no apparent negative effect on glucose tolerance at the end of the study as assessed by an oral glucose tolerance test. Worth noting: this study employed no control group and was a bit short lasting. So let’s look, yet again, for a better study.

One of the first studies on fructose and insulin resistance came in the form of a metabolic ward study in 1972 which examined he effects of high sugar diet compared to a diet with starch in place of sugar, each diet period lasting 10 weeks (33). Most of the subjects had neurological diseases. This time 32% of the calories in the sugar diet came from sucrose, meaning that participants were consuming roughly 80 to 100 grams of fructose every day. Although this diet led to an increase in fasting blood glucose by about 6% compared to the starch diet, when assessed by an oral glucose tolerance test the higher fructose diet did not seem to worsen glucose control:

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1972 must have been a popular year for sugar studies because it was also the year a man named J.I. Mann published a metabolic ward study on 9 healthy men in South Africa (34). When 70 grams of fructose in the diet (from 140 grams of sucrose) was replaced with starch no negative effects on fasting insulin was observed. However, no standardized test of glycemic control was performed and as such this study will be resigned to the ever growing pile of weak studies supporting fructose’s safety in moderate amounts.

A 6 week long study on 42 women found no difference in fasting glucose between a weight loss inducing diet containing roughly 60 grams of fructose and one with about 6 grams of fructose (35).

In 1977 the Mayo clinic conducted two studies on 148 men (36). In the first, 100 grams of fructose per day for 4 days had no effect on fasting glucose levels compared with 50 grams of fructose. They observed no apparent difference in fasting glucose between men with and without coronary artery disease. In the second study 153 grams of fructose per day for 4 days was compared with almost no fructose in men with coronary artery disease. Once again no difference in fasting glucose levels occurred.

The longest trial we have available may be the Turku Sugar study (37). It was a controlled trial which reported that up to 90 grams of fructose in the diet had no consistent effect on fasting insulin or glucose when compared to an equal amount of sucrose or xylitol in Finnish people.

So, while essentially all the previous studies suggest fructose in moderate amounts does not worsen insulin sensitivity, none of these studies employed a euglyemic clamp. Although some used a glucose tolerance test which is a decent test, a euglycemic clamp is considered the best test of insulin sensitivity. Lets look at studies using this assessment of insulin sensitivity.

When 6 children ate more than 100 grams of fructose for one week insulin sensitivity did not change (38). This study being only 7 days long and on children, it may more applicable to kids binging on halloween candy than your average joe trying to avoid type 2 diabetes.

In May of 2013 a trial was conducted in which the effect of a 15% sucrose diet (containing, by my estimates, about 40 to 55 grams of fructose) were compared to a diet with 1/3 the fructose of the other (29). 16 overweight and obese subjects followed these diets for 6 weeks. This study reported no negative effect of the higher fructose diet on insulin sensitivity as measured by euglycemic clamp.

A similar trial on 13 healthy people also reported a higher fructose intake (roughly 90 grams per day) for 6 weeks did not worsen insulin sensitivity as assessed by euglycemic-hyperinsulemic clamp (39). In fact, insulin sensitivity even appeared non-significantly higher in the higher fructose group (25% sucrose). This can be observed at minutes 210-240 in this graph of glucose uptake into primarily skeletal muscle (peripheral tissues) during the clamp:

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In fact, another trial on 7 young men also reported an apparent benefit from a 25% sucrose diet (about 70 grams of fructose). After 30 days on this diet insulin sensitivity as assessed by one of two euglycemic-hyperinsulinemic clamp was significantly better than when the same men ate starch and other carbs instead (40). However, the higher sugar diet had a more favorable fat content: it contained less polyunsaturated fat, which evidence shows could have helped tipped the scales towards better insulin sensitivity.

At this point it seems pretty clear fructose in moderation does not worsen insulin sensitivity compared to starch or other carbohydrates. Of course, the important question now is: what is fructose in moderation? Is it something we can quantify?

Well, it seems about 110 grams of fructose a day is the point at which it begins to exert its toxic effects on insulin control, although one could still expect some variance to this. In my opinion, attempting to replace fructose with other carbohydrates when fructose intake is below about 100 grams will likely do nothing for insulin sensitivity or diabetes risk.

What About Fat?

You may have noticed in the prior section a bit of a discrepancy: I largely ignored the effect of fat, instead looking at the effect of interchanging glucose and fructose or sucrose. Comparing fructose to other carbs like glucose is one thing, but what if you eat fat instead of sugar?

Well, several studies have shown a diet higher in carbs (both fructose and glucose from sugar and glucose from starch) has improved insulin sensitivity (41) or not worsened it (42) compared to higher fat diet.

Unfortunately, there simply isn’t much research on specific fats to make solid statements about the effect of individual fats, but preliminary evidence suggests linoleic acid, a polyunsaturated fat found in vegetable oil, is bad for insulin sensitivity both in general and compared to fructose (43), which could explain the findings of the prior studies.

Saturated and monounsaturated fat could be either better, comparable to, or worse than moderate amounts of fructose but there is essentially no direct evidence available to answer this question. As a result I am not prepared to make any solid statements about how interchanging saturated or monounsaturated fat with fructose might affect insulin sensitivity. Deal with it.

Conclusion

Allow me a moment, if you will, to regurgitate and elucidate the findings from this post with regards to the effect of fructose on insulin sensitivity:

Fructose in moderate doses is fine for diabetics, it may even be beneficial.

Large amounts of fructose (110 grams a day and up) appears to worsen insulin sensitivity compared to other carbohydrates.

Moderate amounts of fructose, around 100 grams a day or less, doesn’t seem to worsen insulin sensitivity in non-diabetics compared to other carbohydrates.

Polyunsaturated fat (for example linoleic acid) seems to be worse for insulin sensitivity than fructose.

Direct evidence comparing fructose with either monounsaturated or saturated fat is lacking.

Now let me further explain the limitations of all that we’ve learned.

Nothing here precludes fructose from having adverse effects on other diseases in doses which I have deemed moderate. Additionally, while fructose/sugar in moderate doses should not worsen insulin sensitivity compared to glucose/starch as a steady state modification, some real world situations may modify this.

Although sugar is not likely inherently fattening, certain foods containing sugar (for example soda) have been shown to promote weight gain, likely due to their high palatability promoting calorie overconsumption. Because getting fat or overeating tends to increase insulin resistance (44, 45), sugar could worsen insulin sensitivity through this mechanism.

Additionally, sugar in the sense of table sugar and high fructose corn syrup have been demonized for their fructose content, but I think the far more dangerous element of these compounds is their near complete lack of any essential nutrients.

It is for these reasons that I think the main source of fructose in the diet should come from fruit.

Not only does fruit intake not seem to promote weight gain, it frequently brings about weight loss (46-48). It also provides a large number of important and/or beneficial vitamins, minerals, and compounds, many of which seem to benefit insulin sensitivity, like magnesium (49-53) and vitamin B1 (54, 55).

For example, eating only 500 calories of numerous fruits (including raspberries, strawberries, cantaloupe, watermelon, and bananas, just to name a few) will provide one with about half of their recommended daily intake of magnesium (a nutrient which I truly believe is by far one of the most important for good insulin sensitivity).

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