This Site is Intended to Discuss the Science of Nutrition and Food. Most articles will be technical in nature.

If you are a layman and if you want to know more about Paleo diet from a Layman point of view, please visit Chennai Paleo Doctor

To Know what to Eat and What not to Eat, please visit Eat Fat Get Thin

Wednesday, 3 August 2016

23 Studies on Low-Carb and Low-Fat Diets

In this article,   has analyzed the data from 23 of these studies comparing low-carband low-fat diets. 
All of the studies are randomized controlled trials, the gold standard of science. All are published in respected, peer-reviewed journals.

Consult Online :

Online Consultation Available at via Web, as well as App

Consult in Person:

All Days, including Weekends
Please Fix Prior Appointments.

-oOo-

7-8 AM, 6-9 PM : Prime Indian Hospital,
1051, Periyar Salai (Poonamalle High Road), Arumbakkam, Opp to New Medical Council, Chennai – 600106.
To Fix Appointments: Call 044 23639999, 9884493140

-oOo-

4-5 PM : GG Super Specialty Hospitals,
21, Dr.Thirumurthy Nagar Main Road, Nungambakkam, Chennai - 600034.
To Fix Appointments: Call 044 28222288
1.Foster GD, et al. A randomized trial of a low-carbohydrate diet for obesity.New England Journal of Medicine, 2003.
Details: 63 individuals were randomized to either a low-fat diet group, or a low-carb diet group. The low-fat group was calorie restricted. This study went on for 12 months.
Weight Loss: The low-carb group lost more weight, 7.3% of total body weight, compared to the low-fat group, which lost 4.5%. The difference was statistically significant at 3 and 6 months, but not 12 months.
Foster, et al. 2003.
Conclusion: There was more weight loss in the low-carb group, significant at 3 and 6 months, but not 12. The low-carb group had greater improvements in blood triglycerides and HDL, but other biomarkers were similar between groups.

2. Samaha FF, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. New England Journal of Medicine, 2003.
Details: 132 individuals with severe obesity (mean BMI of 43) were randomized to either a low-fat or a low-carb diet. Many of the subjects had metabolic syndrome or type II diabetes. The low-fat dieters were calorie restricted. Study duration was 6 months.
Weight Loss: The low-carb group lost an average of 5.8 kg (12.8 lbs) while the low-fat group lost only 1.9 kg (4.2 lbs). The difference was statistically significant.
Samaha, et al. 2003.
Conclusion: The low-carb group lost significantly more weight (about 3 times as much). There was also a statistically significant difference in several biomarkers:
  • Triglycerides went down by 38 mg/dL in the LC group, compared to 7 mg/dL in the LF group.
  • Insulin sensitivity improved on LC, got slightly worse on LF.
  • Fasting blood glucose levels went down by 26 mg/dL in the LC group, only 5 mg/dL in the LF group.
  • Insulin levels went down by 27% in the LC group, but increased slightly in the LF group.
Overall, the low-carb diet had significantly more beneficial effects on weight and key biomarkers in this group of severely obese individuals.

Details: 30 overweight adolescents were randomized to two groups, a low-carb diet group and a low-fat diet group. This study went on for 12 weeks. Neither group was instructed to restrict calories.
Weight Loss: The low-carb group lost 9.9 kg (21.8 lbs), while the low-fat group lost 4.1 kg (9 lbs). The difference was statistically significant.
Sondike, et al. 2003.
Conclusion: The low-carb group lost significantly more (2.3 times as much) weight and had significant decreases in Triglycerides and Non-HDL cholesterol. Total and LDL cholesterol decreased in the low-fat group only.

Details: 53 healthy but obese females were randomized to either a low-fat diet, or a low-carb diet. Low-fat group was calorie restricted. The study went on for 6 months.
Weight Loss: The women in the low-carb group lost an average og 8.5 kg (18.7 lbs), while the low-fat group lost an average of 3.9 kg (8.6 lbs). The difference was statistically significant at 6 months.
Weight Loss Graph, Low Carb vs Low Fat
Conclusion: The low-carb group lost more weight (2.2 times as much) and had significant reductions in blood triglycerides. HDL improved slightly in both groups.

Details: 60 overweight individuals were randomized to a low-carb diet high in monounsaturated fat, or a low-fat diet based on the National Cholesterol Education Program (NCEP).
Both groups were calorie restricted and the study went on for 12 weeks.
Weight Loss: The low-carb group lost an average of 6.2 kg (13.6 lbs), while the low-fat group lost 3.4 kg (7.5 lbs). The difference was statistically significant.
Conclusion: The low-carb group lost 1.8 times as much weight. There were also several changes in biomarkers that are worth noting:
  • Waist-to-hip ratio is a marker for abdominal fat. This marker improved slightly in the LC group, not in the LF group.
  • Total cholesterol improved in both groups.
  • Triglycerides went down by 42 mg/dL in the LC group, compared to 15.3 mg/dL in the LF group.
  • LDL particle size increased by 4.8 nm and percentage of small, dense LDLdecreased by 6.1% in the LC group, while there was no significant difference in the LF group.
Overall, the low-carb group lost more weight and had much greater improvements in several important risk factors for cardiovascular disease.

Details: 120 overweight individuals with elevated blood lipids were randomized to a low-carb or a low-fat diet. The low-fat group was calorie restricted. Study went on for 24 weeks.
Weight Loss: The low-carb group lost 9.4 kg (20.7 lbs) of their total body weight, compared to 4.8 kg (10.6 lbs) in the low-fat group.
Yancy, et al. 2004.
Conclusion: The low-carb group lost significantly more weight and had greater improvements in blood triglycerides and HDL cholesterol.

Details: A randomized, crossover trial with 28 overweight/obese individuals. Study went on for 30 days (for women) and 50 days (for men) on each diet, that is a very low-carb diet and a low-fat diet. Both diets were calorie restricted.
Weight Loss: The low-carb group lost significantly more weight, especially the men. This was despite the fact that they ended up eating more calories than the low-fat group.
Volek, et al. 2004.
Conclusion: The low-carb group lost more weight. The men on the low-carb diet lost three times as much abdominal fat as the men on the low-fat diet.

Details: 40 overweight individuals were randomized to a low-carb and a low-fat diet for 10 weeks. The calories were matched between groups.
Weight Loss: The low-carb group lost 7.0 kg (15.4 lbs) and the low-fat group lost 6.8 kg (14.9 lbs). The difference was not statistically significant.
Conclusion: Both groups lost a similar amount of weight.
A few other notable differences in biomarkers:
  • Blood pressure decreased in both groups, both systolic and diastolic.
  • Total and LDL cholesterol decreased in the LF group only.
  • Triglycerides decreased in both groups.
  • HDL cholesterol went up in the LC group, but decreased in the LF group.
  • Blood sugar went down in both groups, but only the LC group had decreases in insulin levels, indicating improved insulin sensitivity.

Details: 28 overweight premenopausal women consumed either a low-carb or a low-fat diet for 6 weeks. The low-fat group was calorie restricted.
Weight Loss: The women in the low-carb group lost 6.4 kg (14.1 lbs) compared to the low-fat group, which lost 4.2 kg (9.3 lbs). The results were statistically significant.
Conclusion: The low-carb diet caused significantly more weight loss and reduced hunger compared to the low-fat diet.

Details: 102 patients with Type 2 diabetes were randomized to a low-carb or a low-fat diet for 3 months. The low-fat group was instructed to reduce portion sizes.
Weight Loss: The low-carb group lost 3.55 kg (7.8 lbs), while the low-fat group lost only 0.92 kg (2 lbs). The difference was statistically significant.
Conclusion: The low-carb group lost more weight and had greater improvements in the Total cholesterol/HDL ratio. There was no difference in triglycerides, blood pressure or HbA1c (a marker for blood sugar levels) between groups.

Details: 119 overweight individuals were randomized to a low-carb, ketogenic diet or a calorie restricted low-fat diet for 6 months.
Weight Loss: The low-carb group lost 12.9 kg (28.4 lbs), while the low-fat group lost only 6.7 kg (14.7 lbs).
Conclusion: The low-carb group lost almost twice the weight and experienced less hunger.

Details: 311 overweight/obese premenopausal women were randomized to 4 diets: A low-carb Atkins diet, a low-fat vegetarian Ornish diet, the Zone diet and the LEARN diet. Zone and LEARN were calorie restricted.
Weight Loss: The Atkins group lost the most weight at 12 months (4.7 kg – 10.3 lbs) compared to Ornish (2.2 kg – 4.9 lbs), Zone (1.6 kg – 3.5 lbs) and LEARN (2.6 kg – 5.7 lbs). However, the difference was not statistically significant at 12 months.
A to Z Study Weight Loss Graph
Conclusion: The Atkins group lost the most weight, although the difference was not statistically significant. The Atkins group had the greatest improvements in blood pressure, triglycerides and HDL. LEARN and Ornish (low-fat) had decreases in LDL at 2 months, but then the effects diminished.
This study was covered in detail here.

13. Halyburton AK, et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. American Journal of Clinical Nutrition, 2007.
Details: 93 overweight/obese individuals were randomized to either a low-carb, high-fat diet or a low-fat, high-carb diet for 8 weeks. Both groups were calorie restricted.
Weight Loss: The low-carb group lost 7.8 kg (17.2 lbs), while the low-fat group lost 6.4 kg (14.1 lbs). The difference was statistically significant.
Halyburton, et al. 2007.
Conclusion: The low-carb group lost more weight. Both groups had similar improvements in mood, but speed of processing (a measure of cognitive performance) improved further on the low-fat diet.

Details: 13 diabetic and 13 non-diabetic individuals were randomized to a low-carb diet or a “healthy eating” diet that followed the Diabetes UK recommendations (a calorie restricted, low-fat diet). Study went on for 3 months.
Weight Loss: The low-carb group lost 6.9 kg (15.2 lbs), compared to 2.1 kg (4.6 lbs) in the low-fat group.
Dyson, et al. 2007.
Conclusion: The low-carb group lost more weight (about 3 times as much). There was no difference in any other marker between groups.

Details: 84 individuals with obesity and type 2 diabetes were randomized to a low-carb, ketogenic diet or a calorie restricted low-glycemic diet. The study went on for 24 weeks.
Weight Loss: The low-carb group lost more weight (11.1 kg – 24.4 lbs) compared to the low-glycemic group (6.9 kg – 15.2 lbs).
Conclusion: The low-carb group lost significantly more weight than the low-glycemic group. There were several other important differences:
  • Hemoglobin A1c went down by 1.5% in the LC group, compared to 0.5% in the low-glycemic group.
  • HDL cholesterol increased in the LC group only, by 5.6 mg/dL.
  • Diabetes medications were either reduced or eliminated in 95.2% of the LC group, compared to 62% in the low-glycemic group.
  • Many other health markers like blood pressure and triglycerides improved in both groups, but the difference between groups was not statistically significant.

16. Shai I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. New England Journal of Medicine, 2008.
Details: 322 obese individuals were randomized to three diets: a low-carb diet, a calorie restricted low-fat diet and a calorie restricted Mediterranean diet. Study went on for 2 years.
Weight Loss: The low-carb group lost 4.7 kg (10.4 lbs), the low-fat group lost 2.9 kg (6.4 lbs) and the Mediterranean diet group lost 4.4 kg (9.7 lbs).
Shai, et al. 2008.
Conclusion: The low-carb group lost more weight than the low-fat group and had greater improvements in HDL cholesterol and triglycerides.

Details: 107 individuals with abdominal obesity were randomized to a low-carb or a low-fat diet. Both groups were calorie restricted and the study went on for 8 weeks.
Weight Loss: The low-carb group lost 7.9% of body weight, compared to the low-fat group which lost 6.5% of body weight.
Conclusion: The low-carb group lost more weight and there was no difference between groups on Flow Mediated Dilation or any other markers of the function of the endothelium (the lining of blood vessels). There was also no difference in common risk factors between groups.

Details: 88 individuals with abdominal obesity were randomized to a very low-carb or a low-fat diet for 24 weeks. Both diets were calorie restricted.
Weight Loss: The low-carb group lost an average of 11.9 kg (26.2 lbs), while the low-fat group lost 10.1 kg (22.3 lbs). However, the difference was not statistically significant.
Tay, et al. 2008.
Conclusion: The low-carb group lost more weight. Triglycerides, HDL, C-Reactive Protein, Insulin, Insulin Sensitivity and Blood Pressure improved in both groups. Total and LDL cholesterol improved in the low-fat group only.

Details: 40 subjects with elevated risk factors for cardiovascular disease were randomized to a low-carb or a low-fat diet for 12 weeks. Both groups were calorie restricted.
Weight Loss: The low-carb group lost 10.1 kg (22.3), while the low-fat group lost 5.2 kg (11.5 lbs).
Conclusion: The low-carb group lost almost twice the amount of weight as the low-fat group, despite eating the same amount of calories.
This study is particularly interesting because it matched calories between groups and measured so-called “advanced” lipid markers. Several things are worth noting:
  • Triglycerides went down by 107 mg/dL on LC, but 36 mg/dL on the LF diet.
  • HDL cholesterol increased by 4 mg/dL on LC, but went down by 1 mg/dL on LF.
  • Apolipoprotein B went down by 11 points on LC, but only 2 points on LF.
  • LDL size increased on LC, but stayed the same on LF.
  • On the LC diet, the LDL particles partly shifted from small to large (good), while they partly shifted from large to small on LF (bad).

Details: 118 individuals with abdominal obesity were randomized to a low-carb or a low-fat diet for 1 year. Both diets were calorie restricted.
Weight Loss: The low-carb group lost 14.5 kg (32 lbs), while the low-fat group lost 11.5 kg (25.3 lbs) but the difference was not statistically significant.
Brinkworth, et al. 2009.
Conclusion: The low-carb group had greater decreases in triglycerides and greater increases in both HDL and LDL cholesterol, compared to the low-fat group.

Details: 32 obese adults were randomized to a low-carb or a calorie restricted, low-fat diet for 6 weeks.
Weight Loss: The low-carb group lost 6.2 kg (13.7 lbs) while the low-fat group lost 6.0 kg (13.2 lbs). The difference was not statistically significant.
Conclusion: The low-carb group had greater decreases in triglycerides (43.6 mg/dL) than the low-fat group (26.9 mg/dL). Both LDL and HDL decreased in the low-fat group only.

Details: 46 individuals were randomized to a low-carb or a low-fat diet for 36 weeks. Low-fat group was calorie restricted.
Weight Loss: The low-carb group lost more weight and had greater decreases in BMI than the low-fat group.
Krebs, et al. 2010.
Conclusion: The low-carb group had greater reductions in BMI. Various biomarkers improved in both groups, but there was no significant difference between groups.

Details: 61 individuals with type 2 diabetes were randomized to a low-carb or a low-fat diet for 2 years. Both diets were calorie restricted.
Weight Loss: The low-carb group lost 3.1 kg (6.8 lbs), while the low-fat group lost 3.6 kg (7.9 lbs). The difference was not statistically significant.
Conclusion: There was no difference in weight loss or common risk factors between groups. There was significant improvement in glycemic control at 6 months for the low-carb group, but compliance was poor and the effects diminished at 24 months as individuals had increased their carb intake.

Weight Loss

Here is a graph that shows the difference in weight loss between studies. 21 of 23 studies reported weight loss numbers:
Weight Loss on Low-Carb and Low-Fat Diets, Smaller
The majority of studies achieved statistically significant differences in weight loss (always in favor of low-carb). There are several other factors that are worth noting:
  • The low-carb groups often lost 2-3 times as much weight as the low-fat groups. In a few instances there was no significant difference.
  • In most cases, calories were restricted in the low-fat groups, while the low-carb groups could eat as much as they wanted.
  • When both groups restricted calories, the low-carb dieters still lost more weight (71319), although it was not always significant (81820).
  • There was only one study where the low-fat group lost more weight (23) although the difference was small (0.5 kg – 1.1 lb) and not statistically significant.
  • In several of the studies, weight loss was greatest in the beginning. Then people start regaining the weight over time as they abandon the diet.
  • When the researchers looked at abdominal fat (the unhealthy visceral fat) directly, low-carb diets had a clear advantage (5719).
Two of the main reasons why low-carb diets are so effective for weight loss are the high protein content, as well as the appetite-suppressing effects of the diet. This leads to an automatic reduction in calorie intake.
You can read more about why this diet works here: Why do Low Carb Diets Work? The Mechanism Explained

LDL Cholesterol

Despite the concerns expressed by many people, low-carb diets generally do not raise Total and LDL cholesterol levels on average.
Low-fat diets do lower Total and LDL cholesterol, but it is usually only temporary. After 6 to 12 months, the difference is not statistically significant.
There have been some anecdotal reports by doctors who treat patients with low-carb diets, that they can lead to increases in LDL cholesterol and some advanced lipid markers for a small percentage of individuals.
However, none of the studies above noted such adverse effects. The few studies that looked at advanced lipid markers (519) only showed improvements.

HDL Cholesterol

One of the best ways to raise HDL cholesterol levels is to eat more fat. For this reason, it is not surprising to see that low-carb diets (higher in fat) raise HDL significantly more than low-fat diets.
Having higher HDL levels is correlated with improved metabolic health and a lower risk of cardiovascular disease. Having low HDL levels is one of the key symptoms of the metabolic syndrome.
18 of the 23 studies reported changes in HDL cholesterol levels:
HDL Cholesterol on Low-Carb and Low-Fat Diets, Smaller
You can see that low-carb diets generally raise HDL levels, while they don’t change as much on low-fat diets and in some cases go down.

Triglycerides

Triglycerides are an important cardiovascular risk factor and another key symptom of the metabolic syndrome.
The best way to reduce triglycerides is to eat less carbohydrates, especially sugar.
19 of 23 studies reported changes in blood triglyceride levels:
Triglycerides on Low-Carb and Low-Fat Diets, Smaller
It is clear that both low-carb and low-fat diets lead to reductions in triglycerides, but the effect is much stronger in the low-carb groups.

Blood Sugar, Insulin Levels and Type II Diabetes

In non-diabetics, blood sugar and insulin levels improved on both low-carb and low-fat diets and the difference between groups was usually small.
3 studies compared low-carb and low-fat diets in Type 2 diabetic patients.
Only one of those studies had good compliance and managed to reduce carbohydrates sufficiently. This lead various improvements and a drastic reduction in HbA1c, a marker for blood sugar levels (15).
In this study, over 90% of the individuals in the low-carb group managed to reduce or eliminate their diabetes medications.
However, the difference was small or nonexistent in the other two studies, because compliance was poor and the individuals ended up eating carbs at about 30% of calories (1023).

Blood Pressure

When measured, blood pressure tended to decrease on both low-carb and low-fat diets.

How Many People Made it to The End?

A common problem in weight loss studies is that many people abandon the diet and drop out of the studies before they are completed.
I did an analysis of the percentage of people who made it to the end of the study in each group. 19 of the 23 studies reported this number:
Compliance graph, smaller
The average percentage of people who made it to the end of the studies were:
Average for the low-carb groups: 79,51%
Average for the low-fat groups: 77,72%
Not a major difference, but it seems clear from these studies that low-carb diets are at the very least NOT harder to stick to than other diets.
The reason may be that low-carb diets appear to reduce hunger (911) and participants are allowed to eat until fullness.
This is an important point, because low-fat diets are usually calorie restricted and require people to weigh their food and count calories.
Individuals also lose more weight, faster, on low-carb. This may improve motivation to continue on the diet.

Adverse Effects?

Despite the concerns expressed by many health experts in the past, there were zero reports of serious adverse effects that were attributable to either diet.
Overall, the low-carb diet was well tolerated and had an outstanding safety profile.

Tuesday, 2 August 2016

How to Control Type 2 Diabetes Mellitus with Diet Alone

This site will explain the scientific rationale behind Paleo Diet and how to Use that to control Diabetes and "Cure" Obesity


Consult Online :

Online Consultation Available at via Web, as well as App

Consult in Person:

All Days, including Weekends
Please Fix Prior Appointments.

-oOo-

7-8 AM, 6-9 PM : Prime Indian Hospital,
1051, Periyar Salai (Poonamalle High Road), Arumbakkam, Opp to New Medical Council, Chennai – 600106.
To Fix Appointments: Call 044 23639999, 9884493140

-oOo-

4-5 PM : GG Super Specialty Hospitals,
21, Dr.Thirumurthy Nagar Main Road, Nungambakkam, Chennai - 600034.
To Fix Appointments: Call 044 28222288

Wednesday, 27 July 2016

Skinny and 54 kilograms, but with the health hallmarks of obesity

Claire Walker Johnson of Queens, New York, was a medical mystery. No matter how much she ate, she never gained weight.
And yet Johnson, with a long narrow face, had the conditions many obese people develop Type 2 diabetes, high blood pressure, high cholesterol and, most strikingly, a liver buried in fat.

Claire Walker Johnson, a 55-year-old formerly with Type 2 diabetes and a fatty liver, outside her home in New York.
Claire Walker Johnson, a 55-year-old formerly with Type 2 diabetes and a fatty liver, outside her home in New York. Photo: Andrew White/New York Times

She and a very small group of very thin people like her have given scientists surprising clues to one of the most important questions about obesity: Why do fat people often develop serious and sometimes life-threatening medical conditions?
The answer, it turns out, has little to do with the fat itself. It's about each person's ability to store it. With that understanding, scientists are now working on drug treatments to protect people from excess unstored fat and spare them from dire medical conditions.
The need is clear. One in three Americans and one in four adults worldwide have at least three conditions associated with obesity such as diabetes, high cholesterol and high blood pressure - a combination of disorders that doubles their risk of heart attacks and strokes. In addition, two to three per cent of adults in America, or at least 5 million people, have a grave accumulation of fat in their livers caused by obesity that can lead to liver failure.
The detective work that led to this new scientific understanding of fat began with a small group of scientists curious about a disorder that can be caused by a gene mutation so rare it is estimated to affect just one in 10 million people, including, it turned out, Johnson.

For much of her life, Johnson, 55, had no idea anything was amiss. Yes, she was very thin and always ravenous, but in Jamaica, where she was born, many children were skinny, she says, and no one thought much of it. She seemed healthy, and she developed normally through adolescence.
After coming to the United States as a college student, she saw a doctor for some bumps on her arms and was stunned to learn that they were cholesterol crystallising from her blood. Her cholesterol level was sky high.
Further exams revealed that she had other problems fat people can develop - a huge fatty liver, ovarian cysts, extraordinarily high levels of triglycerides.
Johnson's doctor was baffled. The usual instructions to patients to lose weight made no sense in this case. "He said, 'I don't think I can help you,'" she recalled.
She ended up in the office of an endocrinologist, Dr Maria New, who also was stumped but determined to find answers. She measured Johnson: 170 centimetres (5 feet 7 inches). She weighed her: 54 kilograms.
New spent years asking specialists at every medical conference she attended about Johnson. One day in 1996, she was giving a lecture at the National Institutes of Health and posed her usual query: Did anyone know what might be wrong with her skinny patient?
Dr Simeon Taylor, who was chief of the diabetes branch at the National Institute of Diabetes and Digestive and Kidney Diseases, popped up from his chair. He had seen several patients like Johnson. They have lipodystrophy, he said, a rare genetic disorder that is characterised by an abnormal lack of fatty tissue.
Taylor and his colleagues had been studying people with the disorder "as a curiosity," he told New. He was interested in insulin resistance, the cause of Type 2 diabetes, and had assumed it resulted from obesity. But people with lipodystrophy had the most severe insulin resistance he had ever seen, and they were far from obese.
He was hoping to start a study with a new drug, a synthetic version of a hormone called leptin, that might help the patients. The study began in 2000 with Johnson as one of its first participants.
Leptin is released by fat cells and travels through the blood to the brain. The more fat on a person's body, the more leptin is released. When fat levels are low, leptin levels in the brain are low, and the brain responds by increasing the person's appetite, prompting the person to eat and gain weight. For someone like Johnson, who has almost no fat cells to signal the brain, the brain gets almost no leptin. To the brain, it seems as if she is starving. As a result, she receives continuous signals to eat.
With leptin treatment, Johnson's brain was tricked into responding as though she had abundant fat. Her insatiable hunger vanished. Fat disappeared from her liver, her blood glucose became normal, and so did her cholesterol and triglyceride levels.
But why did she and other lipodystrophy patients have these conditions in the first place, and why did they vanish? What was going on?
A couple of studies involving mice produced some clues. Dr Marc Reitman, chief of the diabetes, endocrinology, and obesity branch at the National Institute of Diabetes and Digestive and Kidney Diseases and his colleague, Dr Charles Vinson, of the National Cancer Institute, genetically engineered mice to have lipodystrophy. The mice, like Johnson, had almost no fat tissue. And like her, they developed all of the conditions associated with obesity.
What would happen, the researchers asked, if the mice had a bit more fat tissue?
They transplanted fat tissue into the rodents, and two weeks later, the mice had normal levels of glucose, insulin and triglycerides. Their livers and muscles went back to normal, too.
If that worked, the scientists wondered, could a limitless amount of fat tissue prevent the syndrome, even if copious amounts of fat were stored in that tissue?
Philipp Scherer, director of the Touchstone Diabetes Centre at the University of Texas Southwestern Medical Centre in Dallas, and his colleagues tested the idea. They engineered mice that could make an almost limitless amount of fat tissue. As a result, there was no end to the amount of fat the animals could store. They were, Scherer said, "the fattest mice under the sun, the mouse equivalent of an 800-pound (362 kilo) human being."
The fat mice were metabolically normal.
Now, with years of research, the picture has become clear. And so has a new view of the role of fat itself in causing the medical problems of obesity.
At the heart of all these conditions and what is known as "metabolic syndrome," or having at least three of the conditions associated with obesity, is an inadequate ability to store fat. (Dr C. Ronald Kahn, chief academic officer of the Joslin Diabetes Clinic, said two German physicians called the syndrome "metabolic" nearly 40 years ago. Conditions like elevated cholesterol, diabetes and even high blood pressure appear to be linked through disruptions in metabolism, in this case the abnormal storage of calories.)
The body turns excess food into fat and tries to store it in fat tissue. If there is not enough fat tissue, the fat is stuffed into other organs, like the liver and the heart, as well as the muscles and the pancreas. There it poisons the body, causing metabolic syndrome.
Fat people develop metabolic disorders because their brain is driving them to eat more food than their bodies can store as fat. Their fat tissue has reached its limit. People with lipodystrophy have so little fat tissue that they, too, cannot store the fat their body makes to store extra calories from the food they eat.
This is also why some people find that their metabolic disorders improve with just a small weight loss - they are eating less and their fat tissue can respond properly.
"People traditionally thought of adipose tissue as this inert storage, this white amorphous blob," said Dr Sam Virtue of the University of Cambridge. In fact, he said, "it is a very dynamic organ."
It also explains why 10 to 20 per cent of obese people never develop metabolic disorders, Scherer said. These healthy obese are like his fat mice, with an unusual ability to expand their fat tissue to store calories.
Researchers have moved on to the next phase of the investigation, trying to identify the poison in fat that is causing all these problems and find a way to block it.
At least two chemicals seem to be involved.
Dr Gerald I. Shulman, a Yale professor of medicine and co-director of the Diabetes Research Centre there, and an investigator at the Howard Hughes Medical Institute, has focused on diacylglycerol, produced from fatty acids - made from the food a person eats - and deposited in places like the muscles and liver instead of fat tissue. With diacylglycerol, Shulman found, insulin cannot signal cells. The result is insulin resistance and Type 2 diabetes.
"Diacylglycerol is the culprit," he says. One sure way to get rid of it in liver and muscle cells is to lose weight - to stop providing the body with more calories than its fat tissue can handle, he notes.
That is not so easy. "Every patient I see, I say, 'Let's lose some weight and increase activity.' They all nod their heads. 'That's a great idea.' Maybe one in 100 does it, and even when they are successful, we know how easy it is to gain the weight back."
Shulman is exploring another route, developing benign new variants of a toxic drug that he hopes will be safe and will reduce levels of fat and inflammation in the liver. The drug, dinitrophenol, was once widely used as an over-the counter medication for weight loss, but the Food and Drug Administration took it off the market in 1938 after a few people taking it dropped dead from severely high body temperatures.
He and his colleagues have modified dinitrophenol so, at least in rats, it does not raise body temperature or cause weight loss. But it lowers diacylglycerol levels in the liver and cures Type 2 diabetes and nonalcoholic fatty liver disease, and other metabolic problems associated with obesity.
The problem will be developing it for humans. Would people want to be in a clinical trial using a variant of a drug that originally had potentially lethal side effects?
"This is a proof of concept," Shulman says. "I do think this is a way forward."
Others are focusing on another class of compounds, called ceramides. Scherer, who is studying them, says they are produced from fat floating in the blood and are unable to get into fat tissue for storage or degradation. They, too, cause insulin resistance. Ceramides can also kill cells if their levels become high and can bring on inflammatory responses. And inflammation, Scherer adds, is a hallmark of obesity.
He and others are looking for the best drugs to stanch the activity of enzymes used to make ceramides. Like Shulman, he finds that he can show that his idea works in mice. But, he says, "that's easy to do in a mouse."
All of this raises a provocative question. "It is so accepted that obesity is bad for you, but why is it bad for you?" Virtue says. "If I put a 50-pound (22 kilo) weight on your back and asked you to walk around all day, you would be a superhealthy person."
And that, says Dr Rudolph Leibel of Columbia University, is the beauty of the work on lipodystrophy. People like Johnson have shown a pathway that leads to the diseases of obesity.
"The first step toward curing it is to know why," Leibel says.
The New York Times

Consult Online :

Online Consultation Available at via Web, as well as App

Consult in Person:

All Days, including Weekends
Please Fix Prior Appointments.

-oOo-

7-8 AM, 6-9 PM : Prime Indian Hospital,
1051, Periyar Salai (Poonamalle High Road), Arumbakkam, Opp to New Medical Council, Chennai – 600106.
To Fix Appointments: Call 044 23639999, 9884493140

-oOo-

4-5 PM : GG Super Specialty Hospitals,
21, Dr.Thirumurthy Nagar Main Road, Nungambakkam, Chennai - 600034.
To Fix Appointments: Call 044 28222288