Obesity Doesn't Cause Diabetes--High Blood Sugars Cause Obesity
Scientists have discovered that people don't get Type 2 Diabetes unless several important genes that regulate blood sugar are damaged. Now it's time to explore how this damage causes the obesity so often found in people with diabetes. This research will help you understand why obesity is a symptom of Type 2 diabetes, not its cause. Common wisdom, often repeated by doctors and the media, claims that obesity causes insulin resistance. But it turns out this is not true. Insulin resistance is often genetic and is present long before obesity emerges.
Insulin Resistance Develops in Thin Children of People with Type 2 Diabetes
Lab research has come up with some other intriguing findings that challenge the idea that obesity causes insulin resistance which causes diabetes. Instead, it looks like the opposite happens: Insulin resistance precedes the development of obesity.
One of these studies took two groups of thin subjects with normal blood sugar who were evenly matched for height and weight. The two groups differed only in that one group had close relatives who had developed Type 2 Diabetes, and hence, if there were a genetic component to the disorder, they were more likely to have it. The other group had no relatives with Type 2 Diabetes. The researchers then and examined the subjects' glucose and insulin levels during a glucose tolerance test and calculated their insulin resistance. They found that the thin relatives of the people with Type 2 Diabetes already had much more insulin resistance than did the thin people with no relatives with diabetes.
Insulin resistance in the first-degree relatives of persons with Type 2 Diabetes. Straczkowski M et al. Med Sci Monit. 2003 May;9(5):CR186-90.
This result was echoed by a second study published in November of 2009.
That study compared detailed measurements of insulin secretion and resistance in 187 offspring of people diagnosed with Type 2 diabetes against 509 controls. Subjects were matched with controls for age, gender and BMI. It concluded:
The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.
Beta cell (dys)function in non-diabetic offspring of diabetic patients M. Stadler et al. Diabetologia Volume 52, Number 11 / November, 2009, pp 2435-2444. doi 10.1007/s00125-009-1520-7
Mitochondrial Dysfunction is Found in Lean Relatives of People with Type 2 Diabetes
One reason insulin resistance might precede obesity was explained by a landmark 2004 study which looked at the cells of the "healthy, young, lean" but insulin-resistant relatives of people with Type 2 Diabetes and found that their mitochondria, the "power plant of the cells" that is the part of the cell that burns glucose, appeared to have a defect. While the mitochondria of people with no relatives with diabetes burned glucose well, the mitochondria of the people with an inherited genetic predisposition to diabetes were not able to burn off glucose as efficiently, but instead caused the glucose they could not burn and to be stored in the cells as fat.
Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. Petersen KF et al. New England J Med 2004 Feb 12; 350(7);639-41
More Evidence that Abnormal Insulin Resistance Precedes Weight Gain and Probably Causes It
A study done by the same researchers at Yale University School of Medicine who discovered the mitochondrial problem we just discussed was published in Proceedings of the National Academy of Science (PNAS) in July 2007. It reports on a study that compared energy usage by lean people who were insulin resistant and lean people who were insulin sensitive.
The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndromePetersen,KF et al. PNAS July 31, 2007 vol. 104 no. 31 12587-12594.
Using new imaging technologies, the researchers found that lean but insulin resistant subjects converted glucose from high carbohydrate meals into triglycerides--i.e. fat. Lean insulin-sensitive subjects, in contrast, stored the same glucose in the form of muscle and liver glycogen.
The researchers conclude that:
the insulin resistance, in these young, lean, insulin resistant individuals, was independent of abdominal obesity and circulating plasma adipocytokines, suggesting that these abnormalities develop later in the development of the metabolic syndrome.
In short, obesity looked to be a result, not a cause of the metabolic flaw that led these people to store carbohydrate they ate in the form of fat rather than burn it for energy.
The researchers suggested controlling insulin resistance with exercise. It would also be a good idea for people who are insulin resistant, or have a family history of Type 2 Diabetes to cut back on their carb intake, knowing that the glucose from the carbs they eat is more likely to turn into fat.
Beta Cells Fail to Reproduce in People with Diabetes
A study of pancreas autopsies that compared the pancreases of thin and fat people with diabetes with those of thin and fat normal people found that fat, insulin-resistant people who did not develop diabetes apparently were able to grow new beta-cells to produce the extra insulin they needed. In contrast, the beta cells of people who developed diabetes were unable to reproduce. This failure was independent of their weight.
Beta-Cell Deficit and Increased Beta-Cell Apoptosis in Humans With Type 2 Diabetes.Alexandra E. Butler, et al. Diabetes 52:102-110, 2003
Once Blood Sugars Rise They Impair a Muscle Gene that Regulates Insulin Sensitivity
Another piece of the puzzle falls into place thanks to a research study published on Feb 8, 2008.
Downregulation of Diacylglycerol Kinase Delta Contributes to Hyperglycemia-Induced Insulin Resistance. Alexander V. Chibalin et. al. Cell, Volume 132, Issue 3, 375-386, 8 February 2008.
As reported in Diabetes in Control (which had access to the full text of the study)
The research team identified a "fat-burning" gene, the products of which are required to maintain the cells insulin sensitivity. They also discovered that this gene is reduced in muscle tissue from people with high blood sugar and type 2-diabetes. In the absence of the enzyme that is made by this gene, muscles have reduced insulin sensitivity, impaired fat burning ability, which leads to an increased risk of developing obesity. "The expression of this gene is reduced when blood sugar rises, but activity can be restored if blood sugar is controlled by pharmacological treatment or exercise", says Professor Juleen Zierath. "Our results underscore the importance of tight regulation of blood sugar for people with diabetes."
In short, once your blood sugar rises past a certain point, you become much more insulin resistant. This, in turn, pushes up your blood sugar more.
A New Model For How Diabetes Develops
These research findings open up a new way of understanding the relationship between obesity and diabetes.
Perhaps people with the genetic condition underlying Type 2 Diabetes inherit a defect in the beta cells that make those cells unable to reproduce normally to replace cells damaged by the normal wear and tear of life.Or perhaps exposure to an environmental toxin damages the related genes.
Perhaps, too, a defect in the way that their cells burn glucose inclines them to turn excess blood sugar into fat rather than burning it off as a person with normal mitochondria might do.
Put these facts together and you suddenly get a fatal combination that is almost guaranteed to make a person fat.
Studies have shown that blood sugars only slightly over 100 mg/dl are high enough to render beta cells dysfunctional.
Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Gastaldelli A, et al. Diabetologia. 2004 Jan;47(1):31-9. Epub 2003 Dec 10.
In a normal person who had the ability to grow new beta cells, any damaged beta cells would be replaced by new ones, which would keep the blood sugar at levels low enough to avoid further damage. But the beta cells of a person with a genetic heritage of diabetes are unable to reproduce So once blood sugars started to rise, more beta cells would succumb to the resulting glucose toxicity, and that would, in turn raise blood sugar higher.
As the concentration of glucose in their blood rose, these people would not be able to do what a normal person does with excess blood sugar--which is to burn it for energy. Instead their defective mitochondria will cause the excess glucose to be stored as fat. As this fat gets stored in the muscles it causes the insulin resistance so often observed in people with diabetes--long before the individual begins to gain visible weight. This insulin resistance puts a further strain on the remaining beta cells by making the person's cells less sensitive to insulin. Since the person with an inherited tendency to diabetes' pancreas can't grow the extra beta cells that a normal person could grow when their cells become insulin resistant this leads to ever escalating blood sugars which further damage the insulin-producing cells, and end up in the inevitable decline into diabetes.
Low Fat Diets Promote the Deterioration that Leads to Diabetes in People with the Genetic Predisposition
In the past two decades, when people who were headed towards diabetes begin to gain weight, they were advised to eat a low fat diet. Unfortunately, this low fat diet is also a high carbohydrate diet--one that exacerbates blood sugar problems by raising blood sugars dangerously high, destroying more insulin-producing beta-cells, and catalyzing the storage of more fat in the muscles of people with dysfunctional mitochondria. Though they may have stuck to diets to low fat for weeks or even months these people were tormented by relentless hunger and when they finally went off their ineffective diets, they got fatter. Unfortunately, when they reported these experiences to their doctors, they were almost universally accused of lying about their eating habits.
It has only been documented in medical research during the past two years that that many patients who have found it impossible to lose weight on the low fat high carbohydrate can lose weight--often dramatically--on a low carbohydrate diet while improving rather than harming their blood lipids.
Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. Sharman MJ, et al. J Nutr. 2004 Apr;134(4):880-5.
An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial lipemic responses compared with a low fat diet in normal weight, normolipidemic women.Volek JS, et al. J Nutr. 2003 Sep;133(9):2756-61.
The low carb diet does two things. By limiting carbohydrate, it limits the concentration of blood glucose which often is enough to bring moderately elevated blood sugars down to normal or near normal levels. This means that there will be little excess glucose left to be converted to fat and stored.
It also gets around the mitochondrial defect in processing glucose by keeping blood sugars low so that the body switches into a mode where it burns ketones rather than glucose for muscle fuel.
Relentless Hunger Results from Roller Coaster Blood Sugars
There is one last reason why you may believe that obesity caused your diabetes, when, in fact, it was undiagnosed diabetes that caused your obesity.
Long before a person develops diabetes, they go through a phase where they have what doctors called "impaired glucose tolerance." This means that after they eat a meal containing carbohydrates, their blood sugar rockets up and may stay high for an hour or two before dropping back to a normal level.
What most people don't know is that when blood sugar moves swiftly up or down most people will experience intense hunger. The reasons for this are not completely clear. But what is certain is that this intense hunger caused by blood sugar swings can develop years before a person's blood sugar reaches the level where they'll be diagnosed as diabetic.
This relentless hunger, in fact, is often the very first diabetic symptom a person will experience, though most doctors do not recognize this hunger as a symptom. Instead, if you complain of experiencing intense hunger doctors may suggest you need an antidepressant or blame your weight gain, if you are female, on menopausal changes.
This relentless hunger caused by impaired glucose tolerance almost always leads to significant weight gain and an increase in insulin resistance. However, because it can take ten years between the time your blood sugar begins to rise steeply after meals and the time when your fasting blood sugar is abnormal enough for you to be diagnosed with diabetes, most people are, indeed, very fat at the time of diagnosis.
With better diagnosis of diabetes (discussed here) we would be able to catch early diabetes before people gained the enormous amounts of weight now believed to cause the syndrome. But at least now people with diabetic relatives who are at risk for developing diabetes can go a long way towards preventing the development of obesity by controlling their carbohydrate intake long before they begin to put on weight.
You CAN Undo the Damage
No matter what your genetic heritage or the environmental insults your genes have survived, you can take steps right now to lower your blood sugar, eliminate the secondary insulin resistance caused by high blood sugars, and start the process that leads back to health. The pages linked here will show you how.