What are indications that you might have diabetes or prediabetes?

Diabetes develops very gradually, it could take up to several years. It follows that when you’re in the prediabetes stage, you may not have any symptoms at all. You may, however, notice that: • you eat a standard American processed food diet

or • you’re hungrier than normal
• you’re losing weight, despite eating more
• you’re gaining weight, despite eating less
• you’re thirstier than normal
• you have to go to the bathroom more frequently
• you’re more tired than usual

All of these symptoms are typically associated with diabetes, so if you’re in the early stages of diabetes, you may notice them.

Most patients diagnosed with prediabetes have no idea they have it, it comes as a complete shock!!!!

Are you pre-diabetic? How can you tell? Can it be ignored?? Of all the chronic diseases currently known to mankind, diabetes is the most common. The onset of diabetes starts years before it becomes full-blown and starts affecting one’s health. How can you know if you are on the path to being a full-blown diabetic? What can you do to arrest and reverse this process?

Prediabetes is a “pre-diagnosis” of diabetes—a warning sign of sorts. It happens when your blood glucose level (blood sugar level) is higher than normal but not high enough to be considered diabetes.

Prediabetes is an indication that you could develop type 2 diabetes (T2D) if you don’t take some immediate and lasting lifestyle changes.

During the prediabetes phase, your pancreas still produces enough insulin in response to ingested carbohydrates. The insulin is less effective at removing the sugar from the bloodstream, though, so your blood sugar remains high. This condition is called insulin resistance. Your HgBA1C is greater than 5.6 but less than 6.5. Your fasting sugar is greater than 105.

You should be aggressively treated with lifestyle modification and possibly metformin if you have been diagnosed with prediabetes. A lot of tissue damage is occurring during this silent period.

For Type 2 Diabetes to occur, both insulin resistance and comparative inadequate insulin secretion must co-exist. For example, overweight individuals may have insulin resistance, but diabetes only develops in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance.

Unfortunately, this period of hyperinsulinemia prior to the collapse of insulin production permits is the cause of significant tissue damage.

The problem is that the disease of hyperinsulinemia is highly inflammatory and leads to almost all of the metabolic diseases of Western Society. Treating hyperinsulinemia with more insulin only accelerates the disease.

The correct treatment should be geared to reducing the insulin requirement, by reducing carbohydrate consumption.

Obesity is a threat to U.S. national security, obesity is the leading medical reason why applicants fail to qualify for military service:
27% of young people aged 17 to 24 are too obese to serve in the armed forces.

Over the last 10 years, the number of states with 40 percent of young adults considered by the CDC to be overweight or obese has risen from one state to 39.

When we reverse type 2 diabetes, hyperinsulinemia, and obesity, we are advocating for less medical intervention and more patient self-care.
Empowering the patient to manage a lifestyle disease with a lifestyle intervention does not result in a medical profit.

There is no financial incentive in the Business of Medicine, Big Pharma, or Big Food for this position.

It is obvious that big pharma and big food will not likely be supporting studies that reduce the utilization of their products over non-compensable lifestyle changes. Evidence-based academic research is also unlikely to be performed by academicians who are funded by these same interests. The entire health delivery industry seems to be geared towards medicalization of treatment rather than lifestyle improvement, which would radically disrupt the status quo. “doctors who got money from drug and device makers—even just a meal—prescribed a higher percentage of brand-name drugs overall than doctors who didn’t” and “the more money doctors receive…the more brand-name drugs they tend to prescribe.” Ornstein C, Jones RG, Tigas M. Now there’s proof: docs who get company cash tend to prescribe more brand-name meds. ProPublica. https://www.propublica.org/article/doctors-who-take-company-cash-tend-to-prescribe-more-brand-name-drugs. Published March 17, 2016. Accessed May 1, 2016.

The effects of pharmaceutical firm enticements on physician prescribing patterns. There’s no such thing as a free lunch. J P Orlowski and L Wateska. Chest 1992;102; 270-273 DOI 10.1378/chest.102.1.270

The longer progression to Type 2 Diabetes can be delayed, even if using oral hypoglycemics, the more cost-effective it is. Most physicians wait until someone’s HgBA1C exceeds 6.5, but this is a mistake.

The following is a cost analysis of early intervention with metformin, compared to delaying treatment until insulin supplementation is required due to B-cell fatigue, assuming similar lifestyle management:

The average wholesale cost of generic metformin is less than $0.05/1,000 mg tablet, so a 30-day supply is $6.00 a month.
The average wholesale insulin cost, when a combination of both long-acting and short-acting insulin is prescribed:
Long-acting insulin: Lantus $431/month
Short-acting insulin: Humalog $533/month
Combined cost: $964/month excluding injection supplies.

One could pay for 160 months of metformin therapy for the same cost as 1 month of insulin therapy.

 

Why Treat Obesity and Prediabetes | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

It’s important to treat obesity and prediabetes before diabetes can develop because obesity is the leading indicator in developing diabetes. Data from the National Health and Nutrition Examination Survey reveals that only 12.2 percent of American adults are metabolically healthy.  Eighty-six million adults in the U.S. have prediabetes (HbA1c ranging from 5.7–6.4%), and up to 70 percent of these individuals will eventually develop diabetes.  Obesity is the main factor in the progression of prediabetes to diabetes.

Almost all patients who present to our clinics have significant issues associated with pain, which is one of the hallmarks of metabolic inflammation.  The vast majority of patients who present to our clinics are also overweight, and when we evaluate their biochemical markers, they have prediabetes and metabolic inflammation.  Pre-diabetes is known to be a condition that precedes type 2 diabetes (T2D).  The changes in immune cells’ concentration and function can cause an increased migration of these inflammatory cells to already inflamed tissue. There is also upregulation of cytokines. This immune activation begins during the pre-diabetic state.

The HbA1c has a significant tendency to miss cases of diabetes.  When compared to the oral glucose-tolerance test (OGTT), HbA1c will under-diagnose diabetes in 73 percent of adults.  HbA1c has a sensitivity of 26.93 percent and specificity of 99.39 percent.

The 2019 American Diabetes Association Standards of Medical Care in Diabetes recommends at least yearly screening for those with high risk of prediabetes, stating that patients with “A1C 5.7−6.4% (39−47 mmol/mol)…are ideal candidates for diabetes prevention efforts” as well as that “lifestyle/behavioral therapy featuring an individualized reduced calorie meal plan is highly effective in preventing type 2 diabetes and improving other cardiometabolic markers (such as blood pressure, lipids, and inflammation). ”

• Weight loss utilizing coaching, dietary change, self-efficacy, and increased physical activity can help as well. The recommendation is to “achieve and maintain 7% loss of initial body weight and increase moderate-intensity physical activity (such as brisk walking) to at least 150 min/week.” Additionally, “Metformin therapy for prevention of type 2 diabetes should be considered in those with prediabetes, especially for those with BMI ≥35 kg/m2, those aged <60 years, and women with prior gestational diabetes mellitus.”

They further state that “Prediabetes is associated with heightened cardiovascular risk; therefore, screening for and treatment of modifiable risk factors for cardiovascular disease is suggested.”

Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes—2019; American Diabetes Association. Diabetes Care 2019 Jan; 42(Supplement 1): S29-S33. https://doi.org/10.2337/dc19-S003

Type 2 diabetes is characterized by both peripheral insulin resistance and inadequate insulin production. Insulin resistance has been associated with elevated levels of free fatty acids and proinflammatory cytokines in plasma and leads to decreased glucose transport into muscle cells.

For Type 2 Diabetes to occur, both insulin resistance and inadequate insulin secretion must co-exist. For example, overweight individuals may have insulin resistance, but diabetes only develops in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Unfortunately, this period of prediabetes permits significant tissue damage.

Increased cardiovascular risk begins prior to the development of persistent hyperglycemia, due to insulin resistance (Stern, 1996; Haffner and D’Agostino, 1999).  Macrovascular damage has already occurred with the onset of insulin resistance, while microvascular damage increases with the onset of hyperglycemia.  The United Kingdom Prospective Diabetes Study (UKPDS) analyzed more than 4,000 type 2 diabetes patients who were aggressively treated and followed for up to 15 years. Those in the intensely treated group had a significantly lower rate of progression of microvascular complications than patients receiving standard care. Rates of macrovascular disease were only reduced in the metformin-monotherapy arm, where the risk of myocardial infarction was significantly decreased.

In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, there was a 66 percent increase in mortality per 1 percent increase in HbA1c, with the best outcome for patients maintaining HbA1c below 6.0.

 

Early intervention in the atherogenic prediabetic state, while HbA1c remains in the prediabetic range (5.7-6.4%),  reduces the 200-400 percentage of increased risk of cardiovascular events and plaque formation.  This intervention is cost-effective, low-risk, and disease-modifying if using both lifestyle modification and metformin.  Delaying early intervention (when HbA1c  > 6.5) increases the glycocalyx and endothelial damage and irreversible diabetes-specific microvascular complications.  We readily acknowledge that overly rigorous blood glucose control may have a negative outcome if multiple hypoglycemic agents are used in addition to metformin.  However, the ability to tolerate metformin is excellent if dose escalation is done slowly.

Our early intervention is geared towards lifestyle modification and metformin monotherapy, using the following lifestyle modifications: reducing gastrointestinal permeability from gluten and gliadin, thus reducing the inflammatory load
reducing carbohydrate loading to reduce insulin resistance and fat deposition in the liver, specifical fructose
restoring an appropriate Omega 6:3 ratio by removing industrial seed oils and supplementing with omega-3 fish oil
improving insulin sensitivity by reducing insulin release, using time-restricted feeding, and reducing the overall glycemic load

Metformin

• Metformin has historically been considered a pharmaceutical first-line agent in the treatment of type 2 diabetes, with a very low side effect profile, except for individuals with renal compromise.  Despite the extensive use of metformin, its mechanism of action remains unclear. The following are possibilities when considering how metformin works:
• antibiotic, changing the gut microbiome ratio to a lower proinflammatory load
• effect on the mTOR pathway, which may independently reduce neuropathic pain and is associated with cancer suppression as well as life-lengthening
• change in vagal tone, reducing sympathetic tone and cortisol secretion
• enhances insulin sensitivity at the receptor and lower blood level of insulin
• reduces the formation of advanced glycation end-products
• inhibits the liver’s ability to release glucose into the bloodstream
• inhibits the mitochondrial respiratory chain in the liver, leading to activation of AMPK, enhancing insulin sensitivity (via effects on fat metabolism) and lowering AMP, thus reducing the expression of gluconeogenic enzymes
• inhibition of fructose-1,6-bisphosphatase by AMP in the liver

The longer we can delay progression to Type 2 Diabetes, even if using oral hypoglycemics, the more cost effective it is. The following is a cost analysis of early intervention with metformin, compared to delay in treatment until insulin supplementation is required due to B-cell fatigue, assuming similar lifestyle management:

• The average wholesale cost of generic Metformin is less than $0.05/tablet 1,000 mg, making a 30-day supply $6.00 per month. https://www.goodrx.com/metformin?dosage=1000mg&form=tablet&label_override=metformin&quantity=60
• For an average wholesale insulin cost, a combination of both long-acting and short-acting insulin is prescribed.

Long-acting insulin, Lantus, costs $431/month, and the short-acting insulin, Humalog, costs $533/month, for a combined cost of  $964/month excluding injection supplies.

https://www.goodrx.com/insulins

Someone could pay for 160 months of metformin therapy for the same cost as 1 month of insulin therapy.

Metformin continues to reduce the likelihood of developing type 2 diabetes among those at high risk for it over 15 years, particularly among those with higher baseline glycemia.  Metformin prevents diabetes, which is important because diabetes leads to vision loss, renal failure, amputations, and heart disease.

Preventing or delaying or reducing the risk for diabetes is, is in and of itself, important. Metformin is cheap and well-tolerated with a powerful effect.

Diabetes prevention seen at 15 Years, regardless of analytic method.

Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Prevention Program Research Group. Diabetes Care Apr 2019, 42 (4) 601-608; DOI: 10.2337/dc18-1970

Reversion to normal glucose regulation with reversal of insulin resistance, using early intervention prevents progression of prediabetes to diabetes.  Normalized glucose regulation is an indicator of disease modification, with measurable reduced all-cause mortality.  Our goal is to reduce metabolic inflammation and avoid the preventable complications of insulin resistance.

References for additional reading:

Prevalence of optimal metabolic health is remarkably low among U.S. adults, with one in eight Americans achieving optimal levels of the five traditional cardiometabolic risk factors without medication.

Joana Araújo, Jianwen Cai, and June Stevens. Metabolic Syndrome and Related Disorders. Feb 2019. http://doi.org/10.1089/met.2018.0105

ENDO 2019: The Endocrine Society Annual Meeting.

https://www.endocrine.org/news-room/2019/endo-2019—a1c-test-misses-many-cases-of-diabetes

Prescrire Int. 2014 Nov;23(154):269-72.  https://www.ncbi.nlm.nih.gov/pubmed/25954799

N Engl J Med 2008; 358:2545-2559 https://www.nejm.org/doi/full/10.1056/nejmoa0802743

“Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death (9-63, p=0.017), and 36% for all-cause mortality (9-55, p=0.011).”

Lancet. 1998 Sep 12;352(9131):854-65.  https://www.ncbi.nlm.nih.gov/pubmed/9742977

“The increased risk of adverse cardiovascular outcomes associated with type 2 diabetes does not begin at the diagnostic cutoff for plasma glucose (or HbA1c) at which the condition is diagnosed. Rather, there appears to be a continuum of increased microvascular and macrovascular risk that extends to levels of glycaemia well below these cutoffs. While it seems reasonable to hypothesize that correction of prediabetic dysglycemia might also reduce the future risk of adverse cardiovascular outcomes, further evidence from clinical trials is needed to demonstrate improved long-term outcomes in this setting.”

Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomized controlled clinical trials. Eur J Cardiovasc Prev Rehabil. 2011;18:813–823. [PubMed]

Metformin to be considered in IGT, IFG, HbA1c of 5.7–6.4 %, especially in BMI >35 kg/m², age <60 years or prior GDM

American Diabetes Association Standards of medical care in diabetes—2014. Diabetes Care. 2015;38(Suppl 1):S31–S33.

“As most individuals with prediabetes will eventually go on to develop type 2 diabetes, the large number of people with prediabetes worldwide implies a reservoir of new type 2 diabetes cases to come. Optimizing the management of prediabetes, with the aim of delaying diabetes onset for as long as possible, is therefore an urgent global clinical priority.”

“In the Diabetes Prevention Study (DPS), for example, no patient who achieved at least four of the five lifestyle goals (weight reduction, total fat intake, saturated fat intake, fibre intake, exercise) went on to develop diabetes during the period of follow-up.”

Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care 2012;35:723–730

“The Diabetes Prevention Program (DPP), a randomized controlled clinical trial, demonstrated that compared with the placebo intervention (placebo), the intensive lifestyle intervention (lifestyle) reduced the incidence of type 2 diabetes by 58%, and the metformin intervention (metformin) reduced the incidence of type 2 diabetes by 31% over 2.8 years”

Diabetes Prevention Program Research Group. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012;35:731–737

Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL. Combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the Community Preventive Services Task Force. Ann Intern Med 2015;163:437–451

Knowler WC, Barrett-Connor E, Fowler SE, et al.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403

About GGT (Oracle of Death or The final common Pathway) | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Excess processed foods and carbohydrates can also lead to increased liver damage. GGT isn’t something that people consider when considering health risks, but it could be referred to as the “oracle of death” or “the final common pathway” because of how it predicts liver damage and subsequent disease. Gamma-glutamyl transferase (GGT) is an enzyme found in high concentrations in the liver, and it is elevated in diseases that cause damage to the liver.

GGT is a transferase that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione (GSH) to an acceptor that may be any amino acid, a peptide, or water. GSH removes free radical toxins and provides natural protection against harmful oxidative stress. The normal biologic role of GGT is to reconstitute glutathione, the body’s master antioxidant.

GGT is the only enzyme of the GSH cycle located on the outer surface of the plasma membrane. It breaks down extracellular GSH and provides cysteine, the rate-limiting substrate, for intracellular de novo synthesis of GSH. When GGT concentrations are above “low-normal” ranges, excess GGT can catabolize (degrade) GSH, causing critical depletion of this antioxidant.

When GSH is depleted, oxidative stress and damage start to occur.  This leads to lead to a cycle of the irreversible cell, tissue, and DNA damage, and severe impairment of organ function. Elevated GGT indicates that you are demanding more GSH, and there was not enough GSH in the system to deal with an oxidative insult. During oxidative stress, GGT gene expression is increased, an adaptation to stress.

If you consume excess carbohydrates, processed foods, vegetable oil, alcohol, or other liver toxins, the liver can become insulin resistant, resulting in a high insulin level. Elevated insulin is a metabolic switch that causes fat to accumulate in the liver. Hyperinsulinemia (excess insulin) drives insulin resistance, and insulin resistance encourages more hyperinsulinemia.

As fat accumulates in the liver, the liver becomes more insulin resistant and simultaneously undergoes more oxidative stress, depleting Glutathione, which is reflected by increasing GGT.

 

GGT data was originally collected by the smartest guys in the room (life insurance actuaries), and the original reason for measuring it was its ability to mark alcohol abuse in life insurance applicants. The life insurance industry collected this data for many years, resulting in biometric stratification of mortality risk, and it has now become central to the life insurance underwriting process for predicting all causes of death.

Palmier J., Dixon A., Lanzarth B. Leading Contributors to Mortality Risk in Life Insurance Applicants. Schaumburg, Ill, USA: Society of Actuaries; 2012. (Smalltalk Issue 38).

Palmier J., Lanzrath B. J. Laboratory and biometric predictors of cancer-related mortality in an insured population. Journal of Insurance Medicine. 2012;43(3):162–168

 

Traditionally, elevated GGT has been associated with liver dysfunction, most often alcohol overconsumption. Other drugs that can elevate GGT include barbiturates, phenytoin, anti-inflammatory drugs (including aspirin), St. John’s Wort, and kava.

We now believe that elevated GGT is an early warning sign of other health risks, such as atherosclerosis, stroke, type 2 diabetes, kidney disease, cancer, metabolic syndrome (MetS), and all-cause mortality.

GGT doesn’t have to be above levels considered normal by a laboratory in order to have increased risks. When GGT concentrations exceed the lowest 25% to 35% of normal population ranges, disease risks grow in proportion to increased GGT. This “dose-response” increase in GGT concentration, indicates a greater risk of future diseases and mortality, even when GGT levels are within “normal” ranges.

Even a higher end of normal GGT poses a significant increase in risk:

Normal low

• < 9 U/l for women
• < 14 U/l for men

Moderately high with increased risk

• 18 U/I for women
• 28 U/I for men

High levels of normal with significant increase in risk

• >36 U/L for women
• >56 U/L for men

According to the National Institute of Health, “GGT levels measured in the Framingham Offspring Study (FOS), only moderately elevated GGT, starting at levels just above population GGT medians, and often measured one or two decades in advance of disease endpoints or mortalities, established GGT as an early predictive marker of MetS, CVD, heart failure, and all-cause mortality.”

 

Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

Gerald Koenig, Stephanie Seneff. Dis Markers. 2015; 2015: 818570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620378/

GGT is predictive of future mortality. In the general population, about 21% of men and 15.6% of women have elevated GGT. Elevated GGT, even within normal laboratory ranges, presents significant additional risks.

Patients with a high end of normal  GGT have more than a 1.5-fold risk of dying from cardiovascular diseases in comparison to people with normal low levels of GGT.

All-cause mortality and elevated GGT in the upper fifth of the population levels results in a 2x higher risk for all-cause mortality, 1.7x  higher risk for cardiovascular death, and 2.3x higher risk for cancer and death. Liver cancer and elevated GGT in the upper fifth of the population levels (not even top 1%) results in 15 to 18 times higher risk hepatic cancer and death from liver cancer

Hazard ratios

According to Clinical Chemistry, “GGT above the reference category (GGT ≥9 U/L in women, ≥14 U/L in men) was significantly (P <0.001) associated with all-cause, cancer, hepatobiliary, and vascular mortalities.”

Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver? Lili Kazemi-Shirazi et al. DOI: 10.1373/clinchem.2006.081620 Published April 2007. http://clinchem.aaccjnls.org/content/53/5/940

Elevated levels also result in increased risk for atherogenic dyslipidemia, a predictor of impending heart disease. Dyslipidemia is a reflection of insulin resistance, and when your liver becomes insulin resistant, it will tend to cause visceral fat accumulation in your organs.  Visceral fat accumulation is most noticeably seen as a larger waist than expected, or a “beer belly,” even a small one in women.  Many people are apparently slim, but they are TOFI (thin outside, fat inside).

Dyslipidemia is a combination of high LDL, low HDL, high triglyceride, high particle count of LDL

• LDL:HDL
  Triglyceride:HDL
  LDL-P
  Oxidized LDL
  GGT

 

Most idiopathic or essential hypertension (where they don’t know the cause of the high blood pressure) – is related to hyperinsulinemia with resulting vessel stiffness and thickness.  Reversing hypertension may be as simple as reducing insulin.

GGT correlates with atherosclerotic plaque formation in arteries, which is associated with an inflammatory disease, metainflammation.

GGT activity also co- locates with oxidized LDL in the atherosclerotic plaque, as seen below.

Circulating Markers of Liver Function and Cardiovascular Disease Risk.

Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2290-6. doi: 10.1161/ATVBAHA.115.305235. Epub 2015 May 14.

https://www.ncbi.nlm.nih.gov/pubmed/25977566

Risk for future diabetes:

If your BMI is low and you have a low GGT, you have a baseline risk of 1.0

If you have a low BMI below 25 and a high GGT (in the top quarter of the population), you have a 3x risk of diabetes within 3-5 years

If you have a moderate-high BMI greater than 30 and a high GGT (in the top quarter of the population), you have a 15x risk of diabetes within 3-5 years

If you have a high BMI greater than 35 and a high GGT (in the top quarter of the population), you have a 19x risk of diabetes within 3-5 years

Obesity is one factor that predicts future diabetes, but GGT may be more accurate. If you correct the obesity level for GGT, obesity doesn’t predict diabetes. GGT is more predictive of diabetes as it reflects liver insulin resistance and liver inflammation.

Our treatment protocols for elevated GGT encourage:

• Decompress the fat out of the liver by either time-restricted feeding or fasting
• Eliminate vegetable oil and supplement with fish or krill omega-3 oil
• Switch to natural fats, such as butter and tallow
• Eliminate processed foods, including refined grains and acellular carbohydrates
• Metformin to enhance insulin sensitivity in the liver
• Moderate to high coffee consumption has been universally shown to reduce GGT

Reverse Diabetes MD Presentation | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

It’s time to take a more detailed look at the root causes of obesity, prediabetes, and type 2 diabetes because of the implication for future public health. Reversing the obesity, prediabetes, and type 2 diabetes epidemic is today’s most important public health challenge.  Nearly 70% of population is insulin resistant, prediabetic, or frankly diabetic.

Kraft, J.R.:” Glucose Insulin Tolerance. A routine Clinical Laboratory Tool Enhancing Diabetes Detection”. In O.B. Hunter. Jr. (ed): Radio assay: Clinical Concepts. Skokie, IL. Professional Education Dept. G.D. Searie& Co., 1974. Pp 91-106

Using data from the National Health and Nutrition Examination Survey 2009-2016, less than 12.2% of the US population is now considered metabolically healthy.

“Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009-2016,” was published online Nov. 28 in the journal Metabolic Syndrome and Related Disorders.

Almost all the patients who present to our clinics are overweight, and when we evaluate their biochemical markers, they have prediabetes and metabolic inflammation.  Pre-diabetes is known to be a condition that precedes type 2 diabetes (T2D).  The changes in immune cells concentration and function can cause an increased migration of these inflammatory cells to already inflammed tissue. There is also upregulation of cytokines. This immune activation begins during the pre-diabetic state.

According to studies published in a cardiovascular and heart disease prevention journal in Europe, “The increased risk of adverse cardiovascular outcomes associated with type 2 diabetes does not begin at the diagnostic cutoff for plasma glucose (or HbA1c) at which the condition is diagnosed. Rather, there appears to be a continuum of increased microvascular and macrovascular risk that extends to levels of glycemia well below these cutoffs.”

Hopper I, Billah B, Skiba M, Krum H. Prevention of diabetes and reduction in major cardiovascular events in studies of subjects with prediabetes: meta-analysis of randomized controlled clinical trials. Eur J Cardiovasc Prev Rehabil. 2011;18:813–823. [PubMed]

A 2015 global survey carried out by Credit Suisse revealed a substantial level of misinformation that exists among doctors and nutritionists:

• 92% believed that fat consumption could lead to cardiovascular issues
• 87% believed that fat consumption could lead to obesity
• 54% of doctors and 40% of nutritionists thought that eating cholesterol-rich foods raised blood cholesterol
• 83% of doctors believed butter was worse than margarine
• 66% of doctors believed vegetable oils are beneficial to health.

Fat; The New Health Paradigm – Credit Suisse 2015

The fact that prescription medications are now the third most common cause of death globally after heart disease and cancer should be alarming. The Academy of Medical Royal Colleges and the BMJ provide a blueprint to reduce the harms of “too much medicine” as part of the Choosing Wisely campaign, with recommendations to educate the public to ask their medical professionals whether there are “simpler or safer options” to taking a medication.

Malhotra A, Maughan D, Ansell J, Lehman R, Henderson A, Gray M et al. Choosing Wisely in the UK: The Academy of Medical Royal Colleges’ initiative to reduce the harms of too much medicine BMJ 2015; 350 :h2308.

The root cause of obesity, prediabetes, and type 2 diabetes are embedded in the food environment. Legislative efforts to encourage less consumption of processed foods and sugary drinks will help significantly reduce the burden of diet-related disease, which now contributes to more disease and death globally than physical inactivity, smoking and alcohol combined.

Newton JN, Briggs AD, Murray CJ, Dicker D, Foreman KJ, Wang H, et al. Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015. doi:10.1016/S0140-6736(15)00195-6.

Processed foods labelled as “low-fat” or “proven to lower cholesterol” should be avoided. The flawed science behind the 1977 Dietary Guidelines promoted a reduction in fat consumption, which permitted an increase in carbohydrate consumption.  The shift from natural food containing animal products and fats resulted in an increase in processed food consumption rich in carbohydrates, processed grains, and industrial seed oils. In the United States between 1961-2011, 90% of the increased calorie intake has come from carbohydrates and polyunsaturated vegetable oils.

Select Committee on Nutrition and Human Needs. Dietary goals for the United States. First ed. Washington: U.S. Govt. Print. Off., February 1977.

CreditSuisse.Fat: The New Health Paradigm: Research Institute, 2015: 76

 

The rise in obesity following these guidelines suggest that they may be a root cause of the problem. Nutrition science was originally founded on human correlational studies, which are frequently flawed. But that science has also been corrupted by commercial influences. The undue influence of the food industry on official guideline bodies and politicians has posed a significant threat to public health. “Nutritional epidemiology is a scandal. It should just go to the waste bin,” claims professor John Ioannidis, professor of medicine, health research and policy, and statistics  at Stanford University School of Medicine and School of Humanities and Sciences.

Max Planck also said, “Science progresses one funeral at a time.” it took nearly 50 years from the first published scientific evidence linking smoking and lung cancer until effective regulation was introduced to curb tobacco consumption. Big tobacco companies adopted a strategy of denial, planting doubt, obfuscating, and even buying the loyalty of scientists. The recent similarities with big food and big pharma are uncanny.

Brownell KD, Warner KE. The perils of ignoring history: big tobacco played dirty and millions died. How similar is big food? Milbank Q 2009;87: 259–94.

The food industry has a fiduciary responsibility to produce profit for their shareholders. Unfortunately, the food industries’ downstream cost to public health is bankrupting most westernized societies. Unfortunately, academics, institutions and journals whose primary responsibility is to patients and scientific integrity have at times colluded with industry for financial gain.  It is incredulous to suggest that consuming 22 teaspoons of sugar daily falls within recommended guidelines. This is despite the known science that for optimum health there is no dietary or biological requirement for sugar to be consumed in the human diet.

Malhotra, A. (2013) The dietary advice on added sugar needs emergency surgery. BMJ, 346, f3199.

 

Evidence from multiple randomized controlled trials reveals that a higher-fat, lower-carbohydrate diet is superior to a low-fat diet for weight loss and cardiovascular disease risk reduction. A meta-analysis of 53 randomized controlled trials involving 68,128 participants conducted by the Harvard School of Public Health concluded that “when compared with dietary interventions of similar intensity, evidence from randomized controlled trials does not support low-fat diets over other dietary interventions for long-term weight loss. In weight loss trials, higher-fat weight loss interventions led to significantly greater weight loss than low-fat interventions.”

Sackner-Bernstein J, Kanter D, Kaul S. Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis. PLoS One 2015;10(10):e0139817 DOI: 10.1371/journal.pone.0139817[published Online First: Epub Date]|.

Bazzano LA, Hu T, Reynolds K, et al. Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial Effects of Low-Carbohydrate and Low-Fat Diets. Ann. Intern. Med. 2014;161(5):309-18 DOI: 10.7326/M14-0180[published Online First: Epub Date]|.

Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomized controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2015;2(1) DOI: 10.1136/openhrt-2014-000196[published Online First: Epub Date]|.

 

The Women’s Health Initiative, one of the largest randomized controlled diet trials ever performed, used 48,835 post-menopausal women, with a mean follow-up period of 8.1 years, randomized to either a standard western diet or a low-fat, calorie-reduced diet with increased exercise.   The authors had postulated that a low-fat, calorie-reduced diet with increased exercise would reduce cardiovascular disease. The intervention achieved an 8.2% energy decrease in total fat intake and a 2.9% energy decrease in the saturated fat intake but did not reduce risk of CHD or stroke. The reduction in dietary fat and total daily calories (361 calories/day reduction) failed to produce any significant weight loss over the duration of the study, thus rejecting the hypothesis that the low-fat diet is either beneficial for cardiovascular disease or weight loss.

Howard BV, Van Horn L, Hsia J, et al. Low-fat dietary pattern and risk of cardiovascular disease: The Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 2006;295(6):655-66 doi: 10.1001/jama.295.6.655[published Online First: Epub Date]|.

By contrast, consumption of fat induces satiation and when compared to the other macronutrients such as protein and carbohydrates,  fat has the least impact on blood glucose and insulin production. Excessive insulin production and subsequent insulin resistance is the precursor to type 2 diabetes.  A meta-analysis of the evidence available prior to the 1977 US change in dietary guidelines did not support the dietary fat restrictions. Despite the lack of scientific consensus, these guidelines advised to limit total fat to 30% of calorie intake and saturated fat to 10% of calorie intake, creating the low-fat craze and a national experiment on diet-induced metabolic dysfunction.

Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomized controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart 2015;2(1) doi: 10.1136/openhrt-2014-000196[published Online First: Epub Date]|.

 

Thirty years later, in 2014, a meta-analysis of 76 studies with over 600,000 participants from 18 countries concluded that “Current evidence does not clearly support cardiovascular guidelines that encourage high consumption of polyunsaturated fatty acids and low consumption of total saturated fats.”

Chowdhury R, Warnakula S, Kunutsor S, et al. Association of Dietary, Circulating, and Supplement Fatty Acids With Coronary Risk: A Systematic Review and Meta-analysis. Ann. Intern. Med. 2014;160(6):398-406 doi: 10.7326/M13-1788[published Online First: Epub Date]|.

 

A study published in the BMJ (British Medical Journal) noted that “Saturated fat intake was not associated with all- cause mortality, CVD mortality, total CHD, ischemic stroke, or type 2 diabetes.”

de Souza RJ, Mente A, Maroleanu A, et al. Intake of saturated and trans unsaturated fatty acids and risk of all-cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. BMJ 2015;351 doi: 10.1136/bmj.h3978[published Online First: Epub Date]|.

 

Further, The American Journal of Clinical Nutrition found that “diets with cheese and meat as primary sources of saturated fatty acids cause higher HDL cholesterol and apo A-1 and, therefore, appear to be less atherogenic than is a low-fat, high- carbohydrate diet.”

Thorning TK, Raziani F, Bendsen NT, Astrup A, Tholstrup T, Raben A. Diets with high-fat cheese, high-fat meat, or carbohydrate on cardiovascular risk markers in overweight postmenopausal women: a randomized crossover trial. The American journal of clinical nutrition 2015 doi: 10.3945/ajcn.115.109116[published Online First: Epub Date]|.

 

Full-fat dairy may protect against obesity.  A 2014 study concluded: “Participants in the highest tertile of whole-fat dairy intakes (milk, cheese, yogurt) had significantly lower odds for being obese. “

Crichton GE, Alkerwi Aa. Whole-fat dairy food intake is inversely associated with obesity prevalence: findings from the Observation of Cardiovascular Risk Factors in Luxembourg study. Nutrition Research 2014;34(11):936-43 doi: 10.1016/j.nutres.2014.07.014[published Online First: Epub Date]|.

 

Cohort studies confirm that plasma saturated fatty acids from dairy sources such as cheese and yogurt are inversely related to the incidence of type 2 diabetes. By contrast, the plasma saturated fat palmitic acid, linked to the consumption of starch, sugar and alcohol, is strongly associated with the development of type 2 diabetes.

Mozaffarian D. Saturated fatty acids and type 2 diabetes: more evidence to re-invent dietary guidelines. Lancet Diabetes Endocrinol 2014;2:770–2

Natural, non-processed, non-refined food (meat, fish, eggs, nuts, seeds, olive, avocados) contains high levels of saturated fat. These natural foods are a portion of the ancestral human diet.  People have eaten as much as they want to of these foods without adverse health consequences since paleolithic times, until 1977 when the Dietary guidelines demonized saturated fat of omnipresent natural fat, driving people away from highly nourishing, wholesome and health-promoting foods.

Reducing dietary saturated fats does not reduce cardiovascular events and death. Improvements in cardiovascular outcomes are independent of direct cholesterol lowering. Dietary trials that provide abundant natural fats such as α-linoleic acid, polyphenols and Ω-3 fatty acids found in nuts, olive oil, oily fish and vegetables exert a positive health effect, likely by reducing inflammation, atherosclerosis and thrombosis.

Chakrabarti S, Freedman JE. Review: nutriceuticals as antithrombotic agents. Cardiovasc Ther 2010;28:227–35.

Interestingly, replacing saturated fat with Ω-6 containing vegetable oils (highly processed and refined industrial seed oil) does lower LDL cholesterol but does not actually improve cardiovascular mortality, and may actually increase mortality.

Veerman J Lennert. Dietary fats: a new look at old data challenges established wisdom BMJ 2016; 353 :i1512

Total and LDL cholesterol are a poor marker of cardiovascular health.  Cholesterol profile of elevated triglycerides and low HDL is a more predictive marker of cardiac risk and a reliable marker of insulin resistance. In fact, the QRISK calculator, used to estimate the 10-year risk of CVD, does NOT use LDL cholesterol, but uses total cholesterol/HDL ratio instead.

Preventing insulin resistance in young men would prevent 42% of myocardial infarctions, a larger reduction than correcting hypertension (36%), low high-density lipoprotein cholesterol (31%), body mass index (21%) or low-density lipoprotein cholesterol (16%).

Eddy D, Schlessinger L, Kahn R, Peskin B, Schiebinger R. Relationship of insulin resistance and related metabolic variables to coronary artery disease: a mathematical analysis. Diabetes Care. 2009;32(2):361–6.

 

Refined Carbohydrates:

Prediabetes and Type 2 diabetes are diseases of insulin resistance with initial excessive insulin production, which display the symptom of elevated blood glucose levels as the disease progresses. Treating the root cause of the disease, instead of the symptom, is the key. Eliminate all refined carbohydrates to reverse obesity, prediabetes, and type 2 diabetes.

Refined carbohydrates are known to increase blood glucose levels, increase requirements for medications and result in weight gain. It is disturbing that dietary guidelines prioritize the consumption of starchy carbohydrates for type 2 diabetics, to nearly 55% of their daily macronutrient consumption. Such diets will potentially lead to progressive worsening of disease with all its attendant complications, such as blindness, kidney failure, nerve damage, peripheral vascular disease, heart disease and stroke.

Added sugar has no nutritional value whatsoever. There are no biochemical reactions in the human body that require dietary fructose. No single study exists that demonstrates benefit associated with its consumption.

Credit Suisse – Sugar Consumption at a crossroads

Dietary carbohydrate restriction is the “single most effective intervention for reducing all of the features of the metabolic syndrome” according to Credit Suisse, and should be the first approach in diabetes management. A ketogenic diet (one that comprises less than 10 percent of calorie intake from carbohydrates) results in the greatest falls in HbA1C and reduction in the use of medications. These benefits accrue independently of weight loss.

Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition 2015;31:1–13.

Sugar+veg oil+grain=obesity®PreDM®T2D

Dietary sugar is strongly associated with increased risk of type 2 diabetes, hypertension, and cardiovascular disease, independent of its calories or its effects on body weight.

Lustig RH: Sickeningly sweet: does sugar cause type 2 diabetes? YES. Can J Diab (in press).

Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Erkin-Cakmak A, Gugliucci A, Schwarz JM. Obesity (Silver Spring). 2016 Feb;24(2):453-60. doi: 10.1002/oby.21371. Epub 2015 Oct 26.

Added sugar intake and cardiovascular diseases mortality among US adults. Yang Q, Zhang Z, Gregg EW, Flanders WD, Merritt R, Hu FB. JAMA Intern Med. 2014 Apr;174(4):516-24. doi: 10.1001/jamainternmed.2013.13563.

 

Vegetable Oil:

Despite at least 2-3 million years of human history, only since 1917 have industrial seed oils been a significant part of the human diet, with a major uptick in consumption in the late 1970s. Linoleic acid (the Ω-6 fat in these vegetable oils) is extremely susceptible to oxidation, making foods rancid, but also oxidizing in the body. Linoleic acid, in non-processed whole food (seeds, nuts, fish, and eggs), coexists with vitamins, minerals, and antioxidants, protecting this highly susceptible polyunsaturated fat.

Free Radic Biol Med. 2001 Dec 1;31(11):1388-95. The stomach as a bioreactor: dietary lipid peroxidation in the gastric fluid and the effects of plant derived antioxidants. Kanner J, Lapidot T.

Curr Atheroscler Rep. 2009 Nov;11(6):403-10. Impact of circulating esterified eicosanoids and other oxylipins on endothelial function. Shearer GC, Newman JW.

A meta-analysis including almost 10,000 patients confirmed that high intake of Ω-6 oils (from vegetable oils/margarines) increases the risk of death and heart disease compared to saturated fat plus trans fat. Human research data suggest that we should remove these vegetable oils from our food supply for optimal health.

29.BMJ. 2013 Feb 4;346:e8707. doi: 10.1136/bmj.e8707. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. Ramsden CE1, Zamora D, Leelarthaepin B, Majchrzak-Hong SF, Faurot KR, Suchindran CM, Ringel A, Davis JM, Hibbeln JR.

Older data was confounded by the inclusion of Ω- 3 polyunsaturated fatty acid intake. This misrepresented the health benefits of Ω–6. Other studies, such as the Anti-Coronary Club trial, confirm that Ω–6 PUFA increases death and coronary heart disease compared to animal fat.

Christakis G, Rinzler SH, Archer M t al. Effect of the anti-coronary club program on coronary heart disease. Risk-factor status. JAMA 1966;198:597–604

The LA Veterans trial found that cancer mortality increases with the consumption of Ω–6 rich vegetable oils.

Pearce ML, Dayton S. Incidence of cancer in men on a diet high in polyunsaturated fat. Lancet 1971;1:464-7.

Animal studies have also found that Ω–6 PUFA promotes the growth of experimentally induced cancers, whereas Ω–3 inhibits their growth. Ω–6 rich vegetable oil ( such as sunflower and corn oil), is linked to the increased risk of death, coronary heart disease, and cancer in humans as well as the growth of cancer in animal models.

Am J Epidemiol. 1998 Feb 15;147(4):342-52. Adipose tissue Ω–3 and Ω–6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. Simonsen N1, van’t Veer P, Strain JJ, Martin- Moreno JM, Huttunen JK, Navajas JF, Martin BC, Thamm M, Kardinaal AF, Kok FJ, Kohlmeier L.

Cancer Res. 1988 Dec 1;48(23):6642-7. Effect of different levels of Ω–3 and Ω–6 fatty acids on azoxymethane-induced colon carcinogenesis in F344 rats. Reddy BS, Sugie S.

 

Why eat less, move more fails:

A calorie is a calorie only if it is incinerated in a bomb calorimeter, and the heat given off measured. Biologically derived calories from different foods have entirely different metabolic effects on the human body.  Equal calorie portions of sugar, alcohol, meat or olive oil have widely differing effects on hormonal systems, including insulin and satiety signals such as cholecystokinin or peptide YY. It is irrelevant how many calories a portion of food on a plate contains. What matters is how our body responds to taking in and absorbing those calories, how they are metabolized, and the resulting level of satiety.

The current caloric reduction strategies promoted for weight loss are ineffective. Using the standard calorie reduction approach produces a probability of attaining a normal weight at 1 in 167, generating a greater than 99% failure rate.

Fildes A et al. Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records. Am J Public Health. 2015;105: e54–e59

It is wrongly assumed that excessive caloric intake is the root cause of obesity. A calorie of food energy has different metabolic fates depending upon the hormonal stimulation. That same calorie may be used to generate body heat or stored as body fat. Obesity is a disease of failed energy partitioning, not one of total energy intake. The primary driver of this partitioning is the hormone insulin.  Insulin is specifically a fat storage growth hormone.

Focusing on calories in and calories out produces an inherent bias against high-fat food, which may be protective against obesity and related diseases.  The simplistic calorie focus results in a dietary guideline supportive of starch and sugar replacement of fat, which promotes insulin resistance.

It is our hope that shifting focus away from calories and emphasizing a dietary pattern that focuses on food quality rather than quantity will reduce obesity, related diseases, and cardiovascular risk.

Malhotra A, DiNicolantonio JJ, Capewell S. It is time to stop counting calories, and time instead to promote dietary changes that substantially and rapidly reduce cardiovascular morbidity and mortality. Open Heart 2015;2(1) doi: 10.1136/openhrt-2015-000273[published Online First: Epub Date]|.

Yo-yo dieting with rapid weight loss and regain from fad dieting is detrimental to health. Such ‘weight cycling’ contributes to hypertension, insulin resistance and dyslipidemia, resulting in increased mortality risk and worse cardiovascular outcomes.

Mann T, Tomiyama AJ, Westling E, et al. Medicare’s search for effective obesity treatments: diets are not the answer. Am Psychol 2007;62:220–33.

LC + exercise ¹ health

In the Action for Health in Diabetes trial,  no cardiovascular benefits were found on a low-calorie diet combined with increased physical activity in type 2 diabetic patients.

(Despite the significant weight loss even up to the maximum follow-up of 13.5 years, no health benefits could be found. )

Wing RR, Bolin P, Brancati FL, et al. Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. NEngl J Med 2013;369:145–54.

 

Exercise is not the solution:

It is widely accepted amongst the public and media that consuming more calories than we burn is the cause of the obesity epidemic, and therefore the solution is to just do more exercise.

Food and beverage companies have pushed this physical activity message to exonerate themselves. The very companies promoting processed and highly refined foods linked to the obesity epidemic have sponsored major sporting events.  This association of ultra-processed food and soft drinks with sport is troubling. Celebrity endorsements give the wrong message, particularly to children.

Regular physical activity does have beneficial health effects, but weight loss is not one of them. In fact, there has been little change in our levels of physical activity in the past three decades, while the levels of obesity have increased.

Luke A, Cooper RS. Physical activity does not influence obesity risk: time to clarify the public health message. Int J Epidemiol 2013;42:1831–6.

It is time to bust the myth of physical inactivity and obesity: you cannot outrun a bad diet . A Malhotra, T Noakes, S Phinney Br J Sports Med bjsports- 2015-094911Published Online First: 22 April 2015 doi:10.1136/bjsports-2015- 094911

 

The time spent not eating, is more important than the time spent eating. Snacking will make you fat.  It’s the chronic high insulin from the constant feeding.

There have been two major changes in our dietary habits since the 1970s, prior to the onset of the obesity epidemic. The change to a high-carbohydrate, low-fat diet has been well documented and has played an important role in causing obesity. However, the increase in meal frequency plays an equal if not larger role and has been largely ignored. In the 1970s, the average number of eating opportunities was three – breakfast, lunch and dinner. By 2005, that number had almost doubled. Now we eat breakfast, snack, lunch, snack, dinner and snack — and more often than not, each of these contains refined carbohydrates.

Cameron JD. 6 meals per day does not result in greater weight loss. Br J Nutr. 2010 Apr;103(8):1098-101

Popkin BM. Does hunger and satiety drive eating anymore? Am J Clin Nutr 2010;91:1342–7

 

Eating nearly continuously from the moment we arise to the moment we go to sleep becomes an opportunity to store food energy without a chance to burn it. Eating six times a day does not result in weight loss but tends to increase overall consumption of food.  Snacks are produced for convenience and shelf stability and are filled with refined carbohydrates and often supplemented with Ω–6 vegetable oil.  The hyper-processing of food contributes to a high glycemic index, and the grazing pattern of behavior results in a chronically elevated level of insulin, the fat storage hormone.

Reducing the frequency of our meals and eliminating snacking are simple ideas that were practiced widely before the obesity epidemic.

 

Additional references for RCT’s comparing low carb and low fat for weight loss

• Shai I, et al. Weight loss with a low-carbohydrate, mediterranean, or low-fat diet. N Engl J Med 2008;359(3);229–41.
• Gardner CD, et al. Comparison of the Atkins, Zone, Ornish, and learn Diets for Change in Weight and Related Risk Factors Among Overweight Premenopausal Women. The A to Z Weight Loss Study: A Randomized Trial. JAMA. 2007;297:969–977.
• Brehm BJ, et al. A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women. J Clin Endocrinol Metab 2003;88:1617–1623.
• Samaha FF, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med 2003;348:2074–81.
• Sondike SB, et al. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003 Mar;142(3):253–8.
• Aude YW, et al. The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat. A Randomized Trial. Arch Intern Med. 2004;164:2141–2146.
• Volek JS, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutrition & Metabolism 2004, 1:13.
• Yancy WS Jr, et al. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia. A Randomized, Controlled Trial. Ann Intern Med. 2004;140:769–777.
• Nichols-Richardsson SM, et al. Perceived Hunger Is Lower and Weight Loss Is Greater in Overweight Premenopausal Women Consuming a Low-Carbohydrate/High- Protein vs High-Carbohydrate/Low-Fat Diet. J Am Diet Assoc. 2005;105:1433–1437.
• Krebs NF, et al. Efficacy and Safety of a High Protein, Low Carbohydrate Diet for Weight Loss in Severely Obese Adolescents. J Pediatr 2010;157:252-8.
• Summer SS, et al. Adiponectin Changes in Relation to the Macronutrient Composition of a Weight-Loss Diet. Obesity (Silver Spring). 2011 Mar 31. [Epub ahead of print]
• Daly ME, et al. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes–a randomized controlled trial. Diabet Med. 2006 Jan;23(1):15–20.
• Westman EC, et al. The effect of a low-carbohydrate, ketogenic diet versus a low- glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr. Metab (Lond.)2008 Dec 19;5:36.
• Halyburton AK, et al. Low- and high-carbohydrate weight-loss diets have similar effects on mood but not cognitive performance. Am J Clin Nutr 2007;86:580–7.
• Dyson PA, et al. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects. Diabet Med. 2007 Dec;24(12): 1430-5.
• Keogh JB, et al. Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr 2008;87:567–76.
• Volek JS, et al. Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet. Lipids 2009;44:297–309.
• Partsalaki I, et al. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents. J Pediatr Endocrinol Metab. 2012;25(7-8):697-704.

Dr. Padda explains how he has developed a program to reverse diabetes and how the diabetes industry is profiting from the African-American community.

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