Sickeningly Sweet: Does Sugar Cause Type 2 Diabetes? Yes.

ARTICLE IN PRESS Can J Diabetes xxx (2016) 1–5 Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage: w w w. c a n a d i a n j o u r n a l o f d i a b e t e s . c o m Research Update Sickeningly Sweet: Does Sugar Cause Type 2 Diabetes? Yes Robert H. Lustig MD, MSL Department of Pediatrics, Institute for Health Policy Studies, University of California, San Francisco, San Francisco, California, USA a r t i c l e i n f o Article history: Received 16 December 2015 Accepted 28 January 2016 The metabolic syndrome, of which type 2 diabetes mellitus is a hallmark disease, affects more than 25% of the adult population in the United States (U.S.) (1). Speciﬁcally, type 2 diabetes cur- rently exhibits a U.S. prevalence of 9.3%, while prediabetes is cur- rently estimated to be present in up to 40% of adults. It is assumed that the epidemic rise in obesity is the cause of this upswing in the rate of type 2 diabetes. However, there are 4 separate reasons to doubt this thesis. 1) Although obesity prevalence and diabetes prevalence corre- late, they are not concordant; there are countries in which populations are obese without having diabetes (such as Iceland, Mongolia and Micronesia), and there are countries in which populations have diabetes without being obese (such as India, Pakistan and China, which manifest a 12% diabetes rate). This lack of concordance is further reinforced by looking at years of life lost because of diabetes as opposed to obesity 2) People forget that 20% of morbidly obese individuals are meta- bolically healthy and have normal life spans (4–6), while up to 40% of normal-weight adults harbour metabolic pertur- bations similar to those that occur with obesity, including hypertension, dyslipidemia, nonalcoholic fatty liver disease and cardiovascular disease (7,8). 3) The trend of diabetes in the U.S. between 1988 and 2012 has demonstrated a 25% increase in prevalence in both the obese and the normal-weight populations (9) 4) The aging process does not explain the prevalence of type 2 diabetes; children as young as 1 through 10 years of age now manifest these same biochemical processes (10,11). Thus, although obesity may be a marker for the pathology, it is clearly not the cause because normal-weight people have type 2 diabetes too. So what is the cause, a cause that every- one is exposed to? And how is it that children experience this degree of metabolic dysfunction? The Concept of Toxicity The food industry argues that obesity obeys the ﬁrst law of ther- modynamics, that obesity is about energy balance—that obesity is 1499-2671 © 2016 Canadian Diabetes Association. http://dx.doi.org/10.1016/j.jcjd.2016.01.004 a manifestation of 2 behaviours: increased intake (gluttony) and decreased expenditure (sloth)—and that blame is to be ascribed to the individual, because “a calorie is a calorie.” But obesity is not the issue. Type 2 diabetes is the issue, and a protein calorie is differ- ent from a fat calorie, which is different from a carbohydrate calorie; a calorie is not a calorie (12). Where those calories come from deter- mine where in the body they go. The concept that sugar might be the inciting factor in type 2 diabetes is not new; in fact, John Yudkin of the United Kingdom posited this idea more than 40 years ago (13). However, many people, including scientists, have negative visceral reac- tions to the concept that a food can be toxic. The Merriam-Webster Dictionary deﬁnes toxic as “the degree to which a substance can damage an organism.” Note that there is no distinction between acute and chronic toxicity. Sugar is made of 2 molecules, glucose and fructose. Glucose is the energy of life. Every cell on the planet can burn glucose for energy. Glucose is so important that if one does not consume it, the liver makes it (gluconeogenesis). Con- versely, dietary fructose, while an energy source, is otherwise completely vestigial; there is no biochemical reaction in any ver- tebrate that requires it. Just because something is an energy source does not make it a food. Can you name an energy source that is not nutrition, in which there is no biochemical reaction in the human body (or in any organ- ism) that requires it, that causes disease when consumed at high dosages, yet we love it anyway, and it’s addictive? Answer: alcohol. It’s loaded with calories, but it’s not nutrition. There’s no biochemi- cal reaction that requires it (40% of Americans don’t consume alcohol, and they’re not sick). At high dosages, alcohol causes fatty liver disease. Clearly, alcohol is not a food; it’s a toxin in high dosages. Alcohol is not dangerous because of its calories or its effects on weight. Alcohol is dangerous because it’s alcohol (14); the bio- chemistry of the molecule makes it toxic. There are 2 molecular mechanisms that delineate the toxicity of fructose (Figure 1) (15). 1) Only the liver has the fructose-speciﬁc Glut5 transporter; thus, in the fed state, the overwhelming majority of fructose metabolism occurs in the liver. Fructose is rapidly metabo- lized to fructose-1-phosphate (F1P) via fructokinase, an