Paul Ernsberger, PhD, and Richard J. Koletsky, MD

Obesity and type 2 diabetes

Does excess body fat cause type 2 diabetes? The link between obesity and type 2 diabetes is undeniable. Type 2 diabetes is probably the condition most strongly linked to obesity. One oft-cited statistic is that 80 percent of persons with type 2 diabetes are obese. It is less often mentioned that in the demographic group with the highest incidence of type 2 diabetes, women in their 50s, the overall prevalence of obesity is about 60 percent. Although most prospective studies have found that obese persons are more likely to develop diabetes, there are additional facts to consider (1).

Studies have consistently shown that the disease is genetic in origin. If one identical twin over the age of 50 has type 2 diabetes, there is a 91 percent chance that the second twin will also develop it (2). Although it is true that identical twins share their environment and diet while growing up, by the sixth decade of life, the effect of childhood environment is probably minimal. Furthermore, there was little effect of body mass index (BMI) on the age of onset for diabetes, as the first twin to be diagnosed had an average BMI of 23.8, whereas the second twin, who stayed free of diabetes up to 15 years longer, had an average BMI of 24.9.

Given that type 2 diabetes is a genetic disease, and most of its victims are obese, it follows that the genes causing diabetes must also facilitate weight gain. There is now excellent evidence that this is the case.

Excess levels of insulin are the first abnormality to appear in future diabetics, followed by weight gain. In one study, high insulin levels predicted excess weight gain over the next 17 years (3). People with a family history of diabetes are heavier than those lacking this genetic endowment, and this high-risk group also shows more weight gain over time (4). Also, people with diabetes in their family have higher insulin levels, independent of their body weight (5).

As suggested by the epidemiologist Peter Bennett, “Insulin resistance, rather than obesity, may be the principal determinant of diabetes” (6). Bennett’s model for the development of diabetes is illustrated in Figure 1 [not shown]. Genetic factors initiate the disease process, leading to insulin resistance and a compensatory increase in insulin production by the pancreas. High levels of insulin lead to weight gain, which can further exacerbate insulin resistance. After many years, the system decompensates and blood glucose rises.

Excess body fat is a sign of diabetes risk, but is probably not a direct cause of type 2 diabetes.

Weight Loss and Diabetes

How effective is weight loss as medical treatment for diabetes? Many studies have looked at the short-term benefits of weightloss programs, usually while the participants are still on a restrictive regimen. Here we will only consider those few studies that included at least a 6-month follow-up. For type 2 diabetics, the critical factor to monitor is glycosylated hemoglobin, which provides a picture of the prevailing glucose levels over several weeks.

Many short-term trials show improvement of type 2 diabetes and reduced reliance on pharmacological treatments. A review of controlled trials of weight loss in type 2 diabetes with follow-up of 6 to 18 months showed a deterioration back to starting values, even when weight loss persisted (7). In 21 experimental groups where there was follow-up, persisting benefit was found only in three, despite maintained weight losses of 3 to 9 kg.

A 1-year follow-up study of a behavior modification weight loss program showed that diabetics were actually worse off for having lost weight after 1 year. Overall, it appears that existing very low calorie or behavioral programs have no beneficial effect at 1 year of follow-up, even when weight loss is maintained.

In a prospective study of the relationship between weight change and mortality in type 2 diabetics, those who lost weight had a higher, not lower, risk of death (8). For moderately overweight diabetics (BMI

< 26), successful weight loss led to a tripling of the death rate, although there was a small but significant (16 percent) reduction in death rate associated with weight loss for severely obese diabetics (BMI >

29).

Most prospective studies suggest that weight gain precedes the onset of type 2 diabetes. However, other studies do not show this. In an Israeli prospective study, formerly obese persons had a higher incidence of diabetes (14 percent) than currently obese subjects who had gained weight (6 percent) (9). In every category of current BMI, those who lost weight had a higher risk of developing diabetes than those who gained weight or stayed stable. Among the Pima Indians, who have the highest rate of type 2 diabetes in the world, weight gain is not related to the development of the disease (10).
Despite poor results from weight reduction trials in diabetics, weight loss is still usually considered the cornerstone of diabetes treatment.

Hypertension and Hypercholesterolemia

Hypertension is two to three times more common in obese women and men than in the leanest members of the population (11). Hypercholesterolemia, on the other hand, is only weakly related to body weight. The correlation coefficient between BMI and cholesterol level in most studies is about 0.1 in women and 0.2 in men (12). Blood pressure correlates better with BMI, usually around 0.4 in middle-age (13). Put another way, if you know a woman’s BMI, you can predict her cholesterol level with an accuracy only 1 percent better than pure chance. Blood pressure can be predicted with an accuracy 16 percent better than chance.

Does hypertension result directly from excess body fat? Obesity and hypertension commonly accompany each other in human populations, but the process leading from enlarged fat stores to high blood pressure is unknown.

An animal model of hypertension in obesity was developed at Case Western Reserve University that involves the expression of a specific obesity gene on a background of genetic hypertension (14). In this model, lean and obese siblings are both hypertensive, but the obese animals unexpectedly have somewhat lower blood pressures. Thus, the net impact of genetic obesity on blood pressure is actually protective.

However, if the animals are fed a diet high in salt, blood pressure will rise markedly in the obese rats so that they are more hypertensive than the lean rats. This also happens with weight cycling, wherein the loss of weight on a low-calorie diet is alternated with ad libitum refeeding. Weight-cycled obese rats have very high blood pressures, exceeding those of their lean siblings. Therefore, under nutritional stresses such as excess salt consumption or “yo-yo dieting,” obesity becomes a liability to the cardiovascular system.

Weight stability might distinguish obese rats from obese humans. Obese animals maintain steady body weights and consume a constant amount of food on a day-to-day basis. In contrast, obese humans frequently alternate between fasting and bingeing and show large fluctuations in body weight as they lose and then regain a major proportion of their body fat.

Animals made obese by overfeeding developed hypertension only when subjected to periodic fasts. This effect has been observed in dogs, pigs, mice, and rats, and is more pronounced in genetically obese animals (14). Even though most obese animals have normal blood pressures, when obese animals are made to alternately lose and regain weight, they develop diseases comparable to those experienced by obese humans.

It is well known that for human patients, blood pressure falls immediately following caloric restriction. This has led to guidelines recommending weight loss in hypertensive patients. However, there is little information on long-term changes in blood pressure, particularly during weight regain. A report on the effects of weight regain after therapeutic weight loss showed increases in systolic blood pressure as well as cholesterol, triglycerides, and plasma glucose (15).

The cause of hypertension in obese persons might be the cycles of weight loss and regain they undergo, rather than a direct influence of fat tissue. This would explain the weak relationship between obesity and hypertension in cultures and societies where weight loss practices are uncommon. This “yo-yo hypothesis” requires further testing in human populations.

Weight loss is the most common nondrug treatment recommended for hypertension. However, as is the case with diabetes, the long-term results are disappointing, even when losses are maintained, including massive amounts of weight lost after gastric surgery (13). Promising results have been obtained with trials of multifactorial interventions, which have included exercise, sodium restriction, healthful overall diets, and stress management, along with weight loss (16). It is impossible to say how much of the blood pressure reduction is due to the small loss of body weight (

< 5 kg) that accompanies these lifestyle modifications.

As noted above, cholesterol levels are only weakly correlated with body weight. Indeed, even individuals with so-called “morbid” obesity selected for gastric surgery do not show elevated cholesterol levels (17). The weak relationship between fatness and cholesterol levels can probably be accounted for by dietary factors. A diet high in fat and low in fiber and vegetables can, through separate and independent actions, lead to weight gain and increases in cholesterol. Similarly, a sedentary lifestyle independently promotes weight gain and elevated cholesterol.

The relevant question is where to intervene. We would argue that modification of dietary and exercise habits is a more direct approach and seems more likely to achieve long-term results. Moreover, medications with proven effectiveness are available to treat excessive cholesterol levels.

Heart disease

Type 2 diabetes, hypertension, and elevated cholesterol are primarily of concern because they lead to coronary heart disease, the number one killer in the western world. What is the relationship between obesity and atherosclerosis? The evidence from prospective studies is contradictory.

The Framingham Study, in particular, seems to indicate a higher rate of diagnosed coronary heart disease in obese participants. However, in the Framingham study, weight cycling could account for all of the excess risk associated with obesity (18). Two comprehensive reviews have covered the available literature and concluded that there is no consistent relationship between body weight or body fatness and coronary heart disease (19–20).

Paul Ernsberger, PhD, is an associate professor in nutrition, medicine (hypertension), pharmacology, and neuroscience at Case Western Reserve University School of Medicine in Cleveland, Ohio. With Jeanine C. Cogan, he was co-editor of the Summer 1999 Journal of Social Issues featuring research on weight. Richard J. Koletsky, MD, is an assistant clinical professor of medicine, the director of the Cleveland Weight Wellness Center, and does research at Case Western Reserve University.

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This article is from the Health at Every Size Journal and can be cited as Paul Ernsberger, PhD, and Richard J. Koletsky, MD, “Part 1: Rationale for a Wellness Approach to Obesity” from Health At Every Size 14:1 (January/February 2000).