Tag Archives: insulin resistance

Short-Term Paleo Diet Improves Glucose Control in Obese Type 2 Diabetes (the Masharani Study)

Posted on April 6, 2015 | 3 comments
UCSF is here

UCSF is here

A three-week Paleolithic-style diet improved blood sugars and lipids in obese type 2 diabetics, according to researchers at the University of California—San Francisco. This is the Lynda Frassetto study I’ve been waiting over a year for. The first named author is U. Masharani, so I’ll refer to this work in the future as the Masharani study. Sorry, Lynda.

To understand the impact of this study, you need to know about a blood test called fructosamine, which reflects blood sugar levels over the preceding 2–3 weeks. You may already be familiar with a blood test called hemoglobin A1c: it tells us about blood sugars over the preceding three months. Blood glucose binds to proteins in our blood in a process called glycation. The higher the blood glucose, the more bonding. Glucose bound to hemoglobin molecules is measured in HgbA1c. Glucose bound to plasma proteins (predominantly albumin) is measured as fructosamine. It probably has nothing to do with fructose. Fructosamine is a generic name for plasma ketoamines.

If you’re doing a diabetic diet study over over 2–3 weeks, as in the report at hand, changes in glucose control will mostly be detected in fructosamine rather than HgbA1c levels.

How Was the Research Done?

Twenty-five obese diabetics in the San Francisco Bay area were randomly assigned to either a paleo-style diet or one based on American Diabetes Association (ADA) guidelines. They followed the diets for three weeks, with various measurements taken before and after intervention.

Participants were aged 50-69; you have to guess the sex breakdown. Average body mass index was 34. Over half (63%) were White/European American; there were three each of Asian, African American, and Hispanic ethnicity. They had normal blood pressures and diabetes was well controlled, with hemoglobin A1c’s around 7% and fructosamine levels close to normal. Four subjects were on no diabetes medications; 14 were taking metformin alone, five were on metformin and a sulfonylurea, one was on long-acting insulin and a sulfonylurea. No drug dosages were changed during the study.

Both intervention diets were designed for weight maintenance, i.e., avoidance of weight loss or gain. If participants lost weight, they were instructed to eat more. All food was prepared and provided for the participants. Three meals and three snacks were provided for daily consumption.

Fourteen subjects completed the paleo diet intervention. They ate lean meats, fruits, vegetables, tree nuts, poultry, eggs, canola oil, mayonnaise, and honey. No added salt. No cereal grains, dairy, legumes, or potatoes. Calorie percentages from protein, fat, and carbohydrate were 18%, 27%, and 58%, respectively. Compared to the ADA diet, the paleo diet was significantly lower in saturated fat, calcium, and sodium (under half as much), while higher in potassium (twice as much). These dieters eased into the full paleo diet over the first week, allowing bodies to adjust to higher fiber and potassium consumption. The paleo diet had about 40 grams of fiber, over twice as much as the ADA diet.

[I wonder why they chose canola over other oils.]

Ten subjects completed the ADA diet, which included moderate salt, low-fat dairy, whole grains, rice, bread, legumes, and pasta. Calorie percentages from protein, fat, and carbohydrate were 20%, 29%, and 54%, respectively (very similar to the paleo diet). I don’t have any additional description for you. I assume it included meat, poultry, eggs, and fruit.

Diet compliance was confirmed via urine measurements of sodium, potassium, pH, and calcium.

What Did the Researchers Find?

Both groups on average lost about 2 kg (4-5 lb).

Compared to their baseline values, the paleo group saw reductions in total cholesterol, HDL cholesterol, LDL cholesterol, HgbA1c (down 0.3% absolute reduction), and fructosamine. Fructosamine fell from 294 to 260 micromole/L. [The normal non-diabetic range for fructosamine is 190-270 micromole/L.]

Compared to their baseline values, the ADA diet group saw reductions in HDL cholesterol and HgbA1c (down 0.2% absolute reduction) but no change in fructosamine, total cholesterol, and LDL cholesterol.

Comparing the groups to each other, the difference in fructosamine change was right on the cusp of statistical significance at p = 0.06.

Within each group, insulin resistance trended down, but didn’t reach statistical significance. However, when they looked at the folks who were the most insulin resistant, only the paleo dieters improved their resistance. By the way, insulin resistance was measure via euglycemic hyperinsulinemic clamp instead of the short-cut HOMA-IR method.

Blood pressures didn’t change.

The authors don’t mention hypoglycemia at all, nor alcohol consumption.

They note that some of the paleo dieters complained about the volume of food they had to eat.

Errata

I found what I think are a couple misprints. Table 1 has incorrect numbers for the amount of sodium and potassium in the ADA diet. See the text for correct values. Table 2 give fructosamine values in mg/dl; they should be micromoles/L.

Final Thoughts

This particular version of the paleo diet indeed seems to have potential to help control diabetes in obese type 2’s, perhaps even better than an ADA diet, and despite the high carb content. Obviously, it’s a very small study and I’d like to see it tested in a larger population for several months, and in type 1 diabetics. But it will be years, if ever, before we see those research results. Diabetics alive today have to decide what they’ll eat tomorrow.

I wish the researchers had explained why they chose their paleo diet macronutrient breakdown: calorie percentages from protein, fat, and carbohydrate were 18%, 27%, and 58%, respectively. Perhaps they were trying to match the ratios of the ADA diet. But from what I’ve read, the average ancestral paleo diet carbohydrate energy percentage is 30-35%, not close to 60%. My experience is that reducing carb calorie consumption to 30% or less helps even more with glucose control. Reducing carbs that low in this study would have necessitated diabetes drug adjustments and increased the risk of hypoglycemia.

The authors wonder if the high fiber content of the paleo diet drove the lowered glucose levels.

High HDL cholesterol is thought to be protective against coronary artery disease and other types of atherosclerosis. Both diet groups here saw reductions in HDL. That’s something to keep an eye on.

The ADA diet group saw a drop in HgbA1c but not fructosamine. I can’t explain how HgbA1c goes down over three weeks without a change in fructosamine level.

You have to wonder if the paleo diet results would have been more impressive if the test subjects at baseline had been sicker, with poorly controlled blood pressures and HgbA1c’s of 9% or higher. And it sounds like some of these folks would have lost weight if not forced to eat more. The paleo diet is more satiating than some.

The article was well-written and a pleasure to read, in contrast to some I’ve suffered through recently.

Steve Parker, M.D.

Reference: Masharani, U., et al. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. European Journal of Clinical Nutrition, advance online April 1, 2015. doi: 10.1038/ejcn.2015.39

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Dr. Roy Taylor on the Cause of Type 2 Diabetes and What To Do About It

Posted on January 25, 2014 | 11 comments
diabetic diet, low-carb Mediterranean Diet, low-carb, Conquer Diabetes and Prediabetes

Warning: this is a sciencey post

According to Roy Taylor, M.D., “type 2 diabetes is a potentially reversible metabolic state precipitated by the single cause of chronic excess intraorgan fat.” The organs accumulating fat are the pancreas and liver. He is certain “…that the disease process can be halted with restoration of normal carbohydrate and fat metabolism.” I read Taylor’s article published last year in Diabetes Care.

(Do you remember that report in 2011 touting cure of T2 diabetes with a very low calorie diet? Taylor was the leader. The study involved only 11 patients, eating 600 calories a day for eight weeks.)

Dr. Taylor says that severe calorie restriction is similar to the effect of bariatric surgery in curing or controlling diabetes. Within a week of either intervention, liver fat content is greatly reduced, liver insulin sensitivity returns, and fasting blood sugar levels can return to normal. During the first eight weeks after intervention, pancreatic fat content falls, with associated steadily increasing rates of insulin secretion by the pancreas beta cells.

bariatric surgery, Steve Parker MD

Band Gastric Bypass Surgery (not the only type of gastric bypass): very successful at “curing” T2 diabetes if you survive the operation

Taylor’s ideas, by the way, dovetail with Roger Unger’s 2008 lipocentric theory of diabetes. Click for more ideas on the cause of T2 diabetes.

Here are some scattered points from Taylors article. He backs up most of them with references:

  • In T2 diabetes, improvement in fasting blood sugar reflects improved liver insulin sensitivity more than muscle insulin sensitivity.
  • The more fat accumulation in the liver, the less it is sensitive to insulin. If a T2 is treated with insulin, the required insulin dose is positively linked to how much fat is in the liver.
  • In a T2 who starts insulin injections, liver fat stores tend to decrease. That’s because of suppression of the body’s own insulin delivery from the pancreas to the liver via the portal vein.
  • Whether obese or not, those with higher circulating insulin levels “…have markedly increased rates of hepatic de novo lipogenesis.” That means their livers are making fat. That fat (triglycerides or triacylglycerol) will be either burned in the liver for energy (oxidized), pushed into the blood stream for use elsewhere, or stored in the liver. Fatty acids are components of triglycerides. Excessive fatty acid intermediaries in liver cells—diglycerides and ceramide—are thought to interfere with insulin’s action, i.e., contribute to insulin resistance in the liver.
  • “Fasting plasma glucose concentration depends entirely on the fasting rate of hepatic [liver] glucose production and, hence, on its sensitivity to suppression by insulin.”
  • Physical activity, low-calorie diets, and thiazolidinediones reduce the pancreas’ insulin output and reduce liver fat levels.
  • Most T2 diabetics have above-average liver fat content. MRI scans are more accurate than ultrasound for finding it.
  • T2 diabetics have on average only half of the pancreas beta cell mass of non-diabetics. As the years pass, more beta cells are lost. Is the a way to preserve these insulin-producing cells, or to increase their numbers? “…it is conceivable that removal of adverse factors could result in restoration of normal beta cell number, even late in the disease.”
  • “Chronic exposure of [pancreatic] beta cells to triacylglycerol [triglycerides] or fatty acids…decreases beta cell capacity to respond to an acute increase in glucose levels.” In test tubes, fatty acids inhibit formation of new beta cells, an effect enhanced by increased glucose concentration.
  • There’s a fair amount of overlap in pancreas fat content comparing T2 diabetics and non-diabetics. It may be that people with T2 diabetes are somehow more susceptible to adverse effects of the fat via genetic and epigenetic factors.
  • “If a person has type 2 diabetes, there is more fat in the liver and pancreas than he or she can cope with.”
  • Here’s Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes: “The accumulation of fat in liver and secondarily in the pancreas will lead to self-reinforcing cycles that interact to bring about type 2 diabetes. Fatty liver leads to impaired fasting glucose metabolism and increases export of VLDL triacylglcerol [triglycerides], which increases fat delivery to all tissues, including the [pancreas] islets. The liver and pancreas cycles drive onward after diagnosis with steadily decreasing beta cell function. However, of note, observations of the reversal of type 2 diabetes confirm that if the primary influence of positive calorie balance is removed, the the processes are reversible.”
diabetic diet, etiology of type 2 diabetes, Roy Taylor, type 2 diabetes reversal

Figure 6 from the article: Dr. Taylor’s Twin Cycle Hypothesis of Etiology of Type 2 Diabetes

  • The caption with Figure 6 states: “During long-term intake of more calories than are expended each day, any excess carbohydrate must undergo de novo lipogenesis [creation of fat], which particularly promotes fat accumulation in the liver.”
  • “The extent of weight gloss required to reverse type 2 diabetes is much greater than conventionally advised.” We’re looking at around 15 kg (33 lb) or 20% of body weight, assuming the patient is obese to start.  “The initial major loss of body weight demands a substantial reduction in energy intake. After weight loss, steady weight is most effectively achieved by a combination of dietary restriction and physical activity.”

Dr. Taylor doesn’t specify how much calorie restriction he recommends, but reading between the lines, I think he likes his 600 cals/day for eight weeks program. That will have a have a high drop-out rate. I suspect a variety of existing ketogenic diets may be just as successful and more realistic, even if it takes more than eight weeks. I wonder how many of the 11 “cures” from the 2011 study have persisted.

Steve Parker, M.D.

Reference: Taylor, Roy. Type 2 diabetes: Etiology and reversibility. Diabetes Care, April 2013, vol. 36, no. 4, pp:1047-1055.

Update: Some wild and crazy guys tried the Taylor method at home. Click for results.

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Posted in Causes of Diabetes, Uncategorized, Weight Loss

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Ryberg et al: Effects of Paleolithic Diet on Obese Postmenopausal Women

Posted on June 17, 2013 | 4 comments
Sweden's Flag. Most of the researchers involved with this study are in Sweden

Sweden’s Flag

After menopause, body fat in women tends to accumulate more centrally than peripherally. This is reflected in a higher incidence of fatty liver disease, type 2 diabetes, and cardiovascular disease. A multinational group of researchers wondered if a modified paleo-style diet would have metabolic effects on healthy overweight and obese (BMI 28–35) postmenopausal women in Sweden, with particular attention to fat levels in liver and muscle. I’ll call this the Ryberg study because that’s the first named author.

Study Details

Curiously, they never give the age range of the 10 study participants. Were they closer to 52 or 82?

tuna, fishing, Steve Parker MD, paleo diet, tuna salad

Has anyone even bothered to ask why the tuna are eating mercury? —Jim Gaffigan

The five-week intervention diet seems to have been mostly prepared and provided by the investigators, but they allowed for home cooking by providing menus, recipes, and a food list. No limit on consumption. The goal was to obtain 30% of calories from protein, 40% from fat (mostly unsaturated), and 30% from carbohydrate “…together with 40 g nuts (walnuts and sweet almonds) on a daily basis….”

The diet included lean meat, fish, fruit, vegetables (including root vegetables), eggs and nuts. Dairy products, cereals, beans, refined fats and sugar, added salt, bakery products and soft drinks were excluded.

“They were also advised to use only rapeseed [i.e., canola] or olive oil in food preparation.”

A diet like this should reduce average saturated fat consumption, which was a stated goal, while substituting monounsaturated  and polyunsaturated fat for saturated.

These women were sedentary before and during the intervention.

Results

The ladies indeed made some major changes in their diet. Total calories consumed fell by 22% (2,400 to 1,900 cals). The average weight of participants dropped from 190 lb (86.4 kg) to 180 lb (81.8 kg).

Carbohydrates consumption as a percentage of total calories fell from 49% to 25%. Total carb  grams dropped from 281 to 118, with fiber grams unchanged. To replace some of the carbs, the women increased their protein and fat calorie percentages by about a third. The authors don’t make it clear whether the total carb grams included total fiber grams. (I could probably figure it out if I had the time and inclination, but don’t.) “Before” and “after” fiber grams were 25 and 27, respectively.

In other words, “…the ratio between energy intake from the macronutrients protein, total fat and carbohydrates expressed as E% [calorie percentages] changed significantly from 16:33:50 at baseline to 28:44:25 after five weeks.” Total daily fat grams didn’t change, but the contribution of saturated fat grams fell.

Elevated blood pressure is one component of metabolic syndrome

Elevated blood pressure is one component of metabolic syndrome

A 10-point drop in systolic blood pressure over the five weeks didn’t quite reach statistical significance (p=0.057), but the 9% drop in diastolic pressure did.

“Fasting serum levels of glucose, leptin, cholesterol, triglycerides, HDL, LDL, ApoB and apolipoprotein A1 (ApoA1) and percentage HDL also decreased significantly.”

Fat (or lipid) content of the liver dropped by half. It was measured by magnetic resonance spectroscopy. Peripheral muscle fat content didn’t change, measured in the soleus and  tibialis anterior muscles of the leg.

“Urinary C-peptide excretion and HOMA indices [HOMA1-IR formula] decreased significantly, whereas whole-body insulin sensitivity, measured using the hyperinsulinaemic euglycaemic clamp technique, was not significantly changed.” See footnote labelled PPS at bottom page for confusing details.

My Comments

The intervention diet was a reasonable version of the Paleolithic diet, with one exception. From what I’ve seen from Eaton, Konner, and Cordain, I think they’d agree. Except for the rapeseed oil. It’s fallen out of favor, hasn’t it?

Here’s what the Jaminet’s wrote about canola:

Canola oil…is rapeseed oil bred and processed to remove erucic acid and glucosinolates. During processing, the oil is treated with the solvent hexane and very high temperatures; it may also be subject to caustic refinement, bleaching, and degumming. [Perfect Health Diet, p.225.]

I can’t quite see Grok doing that.

My fantasy about extra virgin olive oil is that it simply oozes out of the olives when pressure is applied. So easy a caveman could do it.

Eaton and Konner have argued that our ancestral diet would have had at least two or three times the fiber as was provided by this diet. But that would have been at a total daily calorie consumption level of at least 3,000 or 3,5oo back in the day. So this diet isn’t so far off.

10-lb Weight Loss Without Calorie Restriction? I'll Take That.

10-lb weight loss In five weeks without conscious calorie restriction? I’ll take that.

The 10 lb (4.6 kg) weight loss is impressive for an eat-all-you-want diet. Calorie intake dropped spontaneously by 500/day, assuming the numbers are accurate. The satiation from higher protein consumption may explain that. The authors admit that the women lost more weight than would be predicted by the energy balance equation (i.e., a pound of fat = 3,500 calories). They wonder about over-estimations of food intake, thermogenic effects of protein versus other macronutrients,  and loss of glycogen (and associated body water). You can’t argue with those scales, though.

While serum C-peptide didn’t fall, urinary levels did. (My sense from reviewing other literature is that 24-hr urine levels of C-peptide are more accurate indicators of insulin production, compared to a single fasting C-peptide level.) The authors interpret this as increased insulin sensitivity in the liver in combination with decreased insulin secretion by the pancreas. Fasting serum insulin levels fell from 8.35 to 6.75 mIU/l (p<0.05).

Regarding the non-significant change in overall insulin sensitivity as judged by hyperinsulinemic euglycemic clamp technique, remember that insulin sensitivity of the liver may be different from sensitivity in peripheral tissues such as muscle. These investigators think that liver insulin sensitivity was clearly improved with their diet.

Blood lipid changes were in the right direction in terms of cardiovascular disease risk, except for the drops in HDL (from 1.35 to 1.17 mmol/l) and ApoA1.

This study may or may not apply to men. Also note the small sample size. Will these results be reproducible in a larger population? In different ethnicities?

I like the reduction in blood pressure. That could help you avoid the risk, expense, and hassle of drug therapy.

From 97 to 90 mg/dl

Serum glucose fell from 96  to 90 mg/dl

I like the drop in fasting blood sugar from 96 to 90 mg/dl (5.35 to 5 mmol/l). It’s modest, but statistically significant. Was it caused by the weight loss, reduced total carb consumption, paucity of sugar and refined starches, lower total calories, higher consumption of protein and mono- and polyunsaturated fats, or a combination of factors? As with most nutritional studies, there’s a lot going on here. A small fasting blood sugar drop like this wouldn’t matter to most type 2 diabetics, but could diabetics see an even greater reduction than these non-diabetics? Only one way to tell: do the study.

I can well imagine this diet curing some cases of metabolic syndrome, prediabetes, mild type 2 diabetes, and fatty liver disease.

Most type 2 diabetics (and prediabetics, for that matter) are overweight or obese.  If a diet like this helps them lose weight, it could improve blood sugar levels. Nearly all authorities recommend that overweight and obese diabetics and prediabetics get their weight down to normal. (I admit that weight loss and improved blood sugar levels are not always in sync.) Weight loss by any standard method tends to improve insulin sensitivity.

Furthermore, the elevated fasting blood sugars that characterize so many cases of diabetes and prediabetes are usually linked to, if not caused by, insulin resistance in the liver. According to these investigators, the diet at hand improves insulin sensitivity in the liver, and even lowers fasting blood sugars in non-diabetic older women.

This modified Paleolithic-style diet doesn’t include table sugar or refined grain starches. That would help control blood sugar levels in both type 1 and type 2 diabetics and prediabetics. The authors didn’t say so, but this must be a relatively low-glcemic-index diet.

The investigators don’t mention ramifications of their diet for folks with diabetes. Their focus is on ectopic fat accumulation (in liver and muscle) and its linkage with insulin resistance and cardiovascular disease. They’ve put together a promising program to try on diabetics or prediabetics. They just need the will and funding to git’r done.

I agree with the authors that the lower calorie consumption, rather than the paleo diet per se, may have caused or contributed to the reduction in liver fat.

Stockholm Palace

Stockholm Palace

The investigators wonder if a Paleolithic-style diet like this would be beneficial over the long-term in patients with non-alcoholic fatty liver disease (NALFD) and associated metabolic disturbance (e.g., impaired sensitivity sensitivity in the liver). NAFLD tends to predict the development of diabetes and cardiovascular disease. If we can prevent or reverse fatty liver, we may prevent or reverse type 2 diabetes and cardiovascular disease, to an extent. You’ll be waiting many years for those clinical study results.

But you have to decide what to eat today.

A significant number of American women (20%?) need to lose weight, lower their blood pressures, lower their blood sugars, and decrease their liver fat. This Ryberg Paleolithic-style diet would probably do it.

A very-low-carb diet is another way to reduce liver fat, and it’s more effective than simple calorie restriction.

Steve Parker, M.D.

Reference: Ryberg, M., et al. A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women. Journal of Internal Medicine, 2013, vol. 274(1), pp: 67-76.  doi: 10.1111/joim.12048

PS: See Carbsane Evelyn for her take on this study here and here.

PPS: Urinary C-peptide secretion reflects insulin production. HOMA is a gauge of insulin resistance, much cheaper and quicker than the purported “gold-standard” hyperinsulinemic euglycemic clamp technique. Why HOMA and the clamp technique in this study didn’t move together is unclear to me, and the authors didn’t explain it. School me in the comment section if you can. Click this HOMA link and you’ll find this statement: “HOMA and clamps yield steady-state measures of insulin secretion and insulin sensitivity in the basal and maximally stimulated states, respectively. HOMA measures basal function at the nadir of the dose-response curve, whereas clamps are an assessment of the stimulated extreme.” Maybe that means HOMA is applicable to the fasted state (no food for 8 hours), whereas the clamp technique is more applicable to the hour or two after you ate half a dozen donuts.

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Do High Insulin Levels Cause Memory Loss and Dementia?

Posted on May 29, 2013 | Comments Off on Do High Insulin Levels Cause Memory Loss and Dementia?
dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss

Don’t wait to take action until it’s too late

Insulin resistance and high blood insulin levels promote age-related degeneration of the brain, leading to memory loss and dementia according to Robert Krikorian, Ph.D. He’s a professor in the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center.  He has an article in a recent issue of Current Psychiatry – Online.

Proper insulin signaling in the brain is important for healthy functioning of our brains’ memory centers.  This signaling breaks down in the setting of insulin resistance and the associated high insulin levels.  Dr. Krikorian makes much of the fact that high insulin levels and insulin resistance are closely tied to obesity.  He writes that:

Waist circumference of ≥100 cm (39 inches) is a sensitive, specific, and independent predictor of hyperinsulinemia for men and women and a stronger predictor than body mass index, waist-to-hip ratio, and other measures of body fat.

Take-Home Points

Dr. Krikorian thinks that dietary approaches to the prevention of dementia are effective yet underutilized.  He mentions reduction of insulin levels by restricting calories or a ketogenic diet: they’ve been linked with improved memory in middle-aged and older adults. His theory is also consistent with the commonly seen association of type 2 diabetes with dementia: overweight and obese type 2’s quite often have high insulin levels, at least in the early years.

Dr. K suggests the following measures to prevent dementia and memory loss:

  • eliminate high-glycemic foods like processed carbohydrates and sweets
  • replace high-glycemic foods with fruits and vegetables (the higher polyphenol intake may help by itself)
  • certain polyphenols, such as those found in berries, may be particularly helpful in improving brain metabolic function
  • keep your waist size under 39 inches (99 cm), or aim for that if you’re higher and overweight

Nearly all popular versions of the paleo diet would qualify as being low glycemic index.

I must mention that many dementia experts, probably most, are not as confident  as Dr. Krikorian that these dietary changes are effective.  I think they are, to a degree.

The Mediterranean diet is high in fruits and vegetables and relatively low-glycemic.  It’s usually mentioned by experts as the diet that may prevent dementia and slow its progression.

Read the full article.

I’ve written before about how blood sugars in the upper normal range are linked to brain degeneration.  Dr. Krikorian’s recommendations would tend to keep blood sugar levels in the lower end of the normal range.

Steve Parker, M.D.

PS: Speaking of dementia and ketogenic, have you ever heard of the Ketogenic Mediterranean Diet?  (Free condensed version here.)

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In T2 Diabetes, Which Comes First: High Insulin Levels or Insulin Resistance?

Posted on April 21, 2013 | 7 comments
pancreas, liver, insulin, woman, teacher, books, diabetes, cause of diabetes

I couldn’t find a decent picture of a liver or pancreas, so this will have to do….

I’ve written elsewhere about the potential causes of T2 diabetes (here and here, for example). There’s a new theory on the block.

Excessive insulin output by the pancreas (hyperinsulinemia) is the underlying cause of type 2 diabetes, according to a hypothesis from Walter Pories, M.D., and G. Lynis Dohm, Ph.D.  The cause of the hyperinsulinemia is a yet-to-be-identified “diabetogenic signal” to the pancreas from the gastrointestinal tract.

This is pretty sciencey, so you’re excused if you stop reading now.  You probably should.

They base their hypothesis on the well-known cure or remission of many cases of type 2 diabetes quite soon after roux-en-y gastric bypass surgery (RYGB) done for weight loss.  (Recent data indicate that six years after surgery, the diabetes has recurred in about a third of cases.)  Elevated fasting insulin levels return to normal within a week of RYGB and remain normal for at least three months.  Also soon after surgery, the pancreas recovers the ability to respond to a meal with an appropriate insulin spike.  Remission or cure of type 2 diabetes after RYGB is independent of changes in weight, insulin sensitivity, or free fatty acids.

Bariatric surgery provides us with a “natural” experiment into the mechanisms behind type 2 diabetes.

The primary anatomic change with RYGB is exclusion of food from a portion of the gastrointestinal tract, which must send a signal to the pancreas resulting in lower insulin levels, according to Pories and Dohm. (RYGB prevents food from hitting most of the stomach and the first part of the small intestine.)

Why would fasting blood sugar levels fall so soon after RYGB?  To understand, you have to know that fasting glucose levels primarily reflect glucose production by the liver (gluconeogenesis).  It’s regulated by insulin and other hormones.  Insulin generally suppresses gluconeogenesis.  The lower insulin levels after surgery should raise fasting glucose levels then, don’t you think?  But that’s not the case.

Pories and Dohm surmise that correction of hyperinsulinemia after surgery leads to fewer glucose building blocks (pyruvate, alanine, and especially lactate) delivered from muscles to the liver for glucose production.  Their explanation involves an upregulated Cori cycle, etc.  It’s pretty boring and difficult to follow unless you’re a biochemist.

The theory we’re talking about is contrary to the leading theory that insulin resistance causes hyperinsulinemia.  Our guys are suggesting it’s the other way around: hyperinsulinemia causes insulin resistance.  It’s a chicken or the egg sort of thing.

If they’re right, Pories and Dohm say we need to rethink the idea of treating type 2 diabetes with insulin except in the very late stages when there may be no alternative.  (I would add my concern about using insulin secretagogues (e.g., sulfonylureas) in that case also.)  If high insulin levels are the culprit, you don’t want to add to them.

We’d also need to figure out what is the source of the “diabetogenic signal” from the gastrointestinal tract to the pancreas that causes hyperinsulinemia.  A number of stomach and intestinal hormones can affect insulin production by the pancreas; these were not mentioned specifically by Pories and Dohm.  Examples are GIP and GLP-1 (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1).

Keep these ideas in mind when you come across someone who’s cocksure that they know the cause of type 2 diabetes.

Steve Parker, M.D.

Reference:  Pories, Walter and Dohm, G. Lynis.  Diabetes: Have we got it all wrong?  Hyperinsulinism as the culprit: surgery provides the evidence.  Diabetes Care, 2012, vol. 35, p. 2438-2442.

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My Critique of the Joslin Critique of the Paleo Diet

Posted on March 16, 2013 | 3 comments
paleo diet, Paleolithic diet, hunter-gatherer diet

Huaorani hunter in Ecuador

The Joslin Diabetes Blog yesterday reviewed the paleo diet as applied to both diabetes and the general public.  They weren’t very favorably impressed with it.  But in view of Joslin’s great reputation, we need to give serious consideration to their ideas.  (I don’t know who wrote the review other than “Joslin Communications.”)

These are the main criticisms:

  • diets omitting grains and dairy are deficient in calcium and possibly B vitamins
  • you could eat too much total and saturated fat, leading to insulin resistance (whether type 1 or 2 diabetes) and heart disease
  • it’s not very practical, partly because it goes against the grain of modern Western cultures
  • it may be expensive (citing the cost of meat, and I’d mention fresh fruit and vegetables, too)

Their conclusion:

There are certainly better diets out there, but if you are going to follow this one, do yourself a favor, take a calcium supplement and meet with a registered dietitian who is also a certified diabetes educator  to make sure it is nutritionally complete, isn’t raising your lipids and doesn’t cause you any low blood glucose incidences.

Expense and Practicality

These take a back seat to the health issues in my view.  Diabetes itself is expensive and impractical.  Expense and practicality are highly variable, idiosyncratic matters to be pondered and decided by the individual.  If there are real health benefits to the paleo diet, many folks will find work-arounds for any expense and impracticality.  If the paleo diet  allows use of fewer drugs and helps avoid medical complications, you save money in health care costs that you can put into food.  Not to mention quality of life issues (but I just did).

Calcium and B Vitamin Deficiencies

This is the first I’ve heard of possible B vitamin deficiencies on the paleo diet.  Perhaps I’m not as well-read as I thought.  I’ll keep my eyes open for confirmation.

The potential calcium deficiency, I’ve heard of before.  I’m still open-minded on it.  I am starting to wonder if we need as much dietary calcium as the experts tell us.  The main question is whether inadequate calcium intake causes osteoporosis, the bone-thinning condition linked to broken hips and wrists in old ladies.  This is a major problem for Western societies.  Nature hasn’t exerted much selection pressure against osteoporosis because we don’t see most of the fractures until after age 70.  I wouldn’t be surprised if we eventually find that life-long exercise and adequate vitamin D levels are much more important that calcium consumption.

With regards to calcium supplementation, you’ll find several recent scientific references questioning it.  For example, see this, and this, and this, and this, and this.  If you bother to click through and read the articles, you may well conclude there’s no good evidence for calcium supplementation for the general population.  If you’re not going to supplement, would high intake from foods be even more important?  Maybe so, maybe not.  I’m don’t know.

If you check, most of the professional osteoporosis organizations are going to recommend calcium supplements for postmenopausal women, unless dietary calcium intake is fairly high.

If I were a women wanting to avoid osteoporosis, I’d do regular life-long exercise that stressed my bones (weight-bearing and resistance training) and be sure I had adequate vitamin D levels.  And men, you’re not immune to osteoporosis, just less likely to suffer from it.

Insulin Resistance

Insulin resistance from a relatively high-fat diet is theoretically possible.  In reality, it’s not common.  I’ve read plenty of low-carb high-fat diet research reports in people with type 2 diabetes.  Insulin levels and blood glucose levels go down, on average.  That’s not what you’d see with new insulin resistance.  One caveat, however, is that these are nearly all short-term studies, 6-12 weeks long.

If you have diabetes and develop insulin resistance on a high-fat diet, you will see higher blood sugar levels and the need for higher insulin drug doses.  Watch for that if you try the paleo diet.

Are High Total and Saturated Fat Bad?

Regarding relatively high consumption of total and saturated fat as a cause of heart or other vascular disease: I don’t believe that any more.  Click to see why.  If you worry about that issue, choose meats that are leaner (lower in fat) and eat smaller portions.  You could also look at your protein foods—beef, chicken, fish, eggs, offal, etc.—and choose items lower in total and saturated fat.  Consult a dietitian or online resource.  Protein deficiency is rarely, if ever, a problem on paleo diets.

In Conclusion

I think the paleo diet has more healthful potential than realized by the Joslin blogger(s).  I’m sure they’d agree we need more clinical studies of it, involving both type 1 and 2 diabetics.  I appreciate the “heads up” regarding potential vitamin B deficiencies.  My sense is that the Joslin folks are willing to reassess their position based on scientific studies.

I bet some of our paleo-friendly registered dietitians have addressed the potential adverse health issues of the paleo diet.  Try Amy Kubal, Franziska Spritzler (more low-carb than paleo) or Aglaée Jacob.  I assume the leading paleo diet book authors have done it also.

If you’re worried about adverse blood lipid changes on the paleo diet, get them tested before you start, then after two months of dieting.

Steve Parker, M.D.

PS: The paleo diet is also referred to as the Stone Age diet, caveman diet, Paleolithic diet, hunter-gatherer diet, and ancestral diet.

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What Causes Type 2 Diabetes?

Posted on January 26, 2013 | Comments Off on What Causes Type 2 Diabetes?

“Beats me. I teach math!”

There’s no simple answer, unfortunately.

You can lower your risk of type 2 diabetes significantly by avoiding overweight and obesity, by exercising regularly, and by choosing the right parents.  These provide clues as to the causes of diabetes.  The Mediterranean diet also prevents diabetes.

UpToDate.com offers a deceptively simple answer:

Type 2 diabetes mellitus is caused by a combination of varying degrees of insulin resistance and relative insulin deficiency. [Insulin is the pancreas hormone that lowers blood sugar.] Its occurrence most likely represents a complex interaction among many genes and environmental factors, which are different among different populations and individuals.

So, what causes the insulin resistance and relative insulin deficiency?

Understanding the pathogenesis [cause] of type 2 diabetes is complicated by several factors. Patients present with a combination of varying degrees of insulin resistance and relative insulin deficiency, and it is likely that both contribute to type 2 diabetes. Furthermore, each of the clinical features can arise through genetic or environmental influences, making it difficult to determine the exact cause in an individual patient. Moreover, hyperglycemia itself can impair pancreatic beta cell function and exacerbate insulin resistance, leading to a vicious cycle of hyperglycemia causing a worsening metabolic state.

The UpToDate article then drones on, discussing mouse studies, various genes, free fatty acids, adiponectin, leptin, amylin, insulin secretion, insulin resistance, impaired insulin processing, insulin action, body fat distribution, inflammation, various inflammatory markers, low birth weight, high birth rate, prematurity, etc.

More excerpts:

Increased free fatty acid levels, inflammatory cytokines from fat, and oxidative factors, have all been implicated in the pathogenesis of metabolic syndrome, type 2 diabetes, and their cardiovascular complications.

Insulin resistance may, at least in part, be related to substances secreted by adipocytes [fat cells] (“adipokines” including leptin adiponectin, tumor necrosis factor alpha, and resistin).

Type 2 diabetes most likely represents a complex interaction among many genes and environmental factors.

That’s the simplest answer I can give now.

Steve Parker, M.D.

Reference: “The Pathogensis of Type 2 Diabetes Mellitus”  by David K McCulloch, MD, and R Paul Robertson, MD, at UpToDate.com, updated June 2012, and accessed November 19, 2012.

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What’s Wrong With Type 2 Diabetics?

Posted on December 2, 2012 | Comments Off on What’s Wrong With Type 2 Diabetics?

Type 2 diabetes and prediabetes are epidemics because of excessive consumption of refined sugars and starches, and lack of physical activity.  I can’t prove it; nevertheless that’s my impression after years of reading the nutrition science literature and thinking about it.

I could be wrong.  I reserve the option to change my mind based on evidence as it becomes available.  That’s one of the great things about science.  Accurately identifying the cause of diabetes could provide strong clues about optimal prevention and treatment strategies.

Genetics undoubtedly plays a major role in diabetes, but the gene pool hasn’t changed much over the last several decades as type 2 diabetes rates have soared.

The problem in type 2 diabetes and prediabetes is that the body cannot handle ingested carbohydrates in the normal fashion. In a way, dietary carbohydrates (carbs) have become toxic instead of nourishing. This is a critical point, so let’s take time to understand it.

NORMAL DIGESTION AND CARBOHYDRATE HANDLING

The major components of food are proteins, fats, and carbohydrates. We digest food either to get energy, or to use individual components of food in growth, maintenance, or repair of our own body parts.

We need some sugar (also called glucose) in our bloodstream at all times to supply us with immediate energy. “Energy” refers not only to a sense of muscular strength and vitality, but also to fuel for our brain, heart, and other automatic systems. Our brains especially need a reliable supply of bloodstream glucose.

In a normal, healthy state, our blood contains very little sugar—about a teaspoon (5 ml) of glucose. (We have about one and a third gallons (5 liters) of blood circulating. A normal blood sugar of 100 mg/dl (5.56 mmol/l) equates to about a teaspoon of glucose in the bloodstream.)

Our bodies have elaborate natural mechanisms for keeping blood sugar normal. They work continuously, a combination of adding and removing sugar from the bloodstream to keep it in a healthy range (70 to 140 mg/dl, or 3.9 to 7.8 mmol/l). These homeostatic mechanisms are out of balance in people with diabetes and prediabetes.

By the way, glucose in the bloodstream is commonly referred to as “blood sugar,” even though there are many other types of sugar other than glucose. In the U.S., blood sugar is measured in units of milligrams per deciliter (mg/dl), but other places measure in millimoles per liter (mmol/l).

When blood sugar levels start to rise in response to food, the pancreas gland—its beta cells, specifically—secrete insulin into the bloodstream to keep sugar levels from rising too high. The insulin drives the excess sugar out of the blood, into our tissues. Once inside the tissues’ cells, the glucose will be used as an immediate energy source or stored for later use. Excessive sugar is stored either as body fat or as glycogen in liver and muscle.

When we digest fats, we see very little direct effect on blood sugar levels. That’s because fat contains almost no carbohydrates. In fact, when fats are eaten with high-carb foods, they tend to slow the rise and peak in blood sugar you would see if you had eaten the carbs alone.

Ingested protein can and does raise blood sugar, usually to a mild degree. As proteins are digested, our bodies can make sugar (glucose) out of the breakdown products. The healthy pancreas releases some insulin to keep the blood sugar from going too high.

In contrast to fats and proteins, carbohydrates in food cause significant—often dramatic—rises in blood sugar. Our pancreas, in turn, secretes higher amounts of insulin to prevent excessive elevation of blood glucose. Carbohydrates are easily digested and converted into blood sugar. The exception is fiber, which is indigestible and passes through us unchanged.

During the course of a day, the pancreas of a healthy person produces an average of 40 to 60 units of insulin. Half of that insulin is secreted in response to meals, the other half is steady state or “basal” insulin. The exact amount of insulin depends quite heavily on the amount and timing of carbohydrates eaten. Dietary protein has much less influence. A pancreas in a healthy person eating a very-low-carb diet will release substantially less than 50 units of insulin a day.

To summarize thus far: dietary carbs are the major source of blood sugar for most people eating “normally.” Carbs are, in turn, the main cause for insulin release by the pancreas, to keep blood sugar levels in a safe, healthy range.

Hang on, because we’re almost done with the basic science!

You deserve a break

CARBOHYDRATE  HANDLING  IN  DIABETES  &  PREDIABETES

Type 2 diabetics and prediabetics absorb carbohydrates and break them down into glucose just fine. Problem is, they can’t clear the glucose out of the bloodstream normally. So blood sugar levels are often in the elevated, poisonous range, leading to many of the complications of diabetes.

Remember that insulin’s primary function is to drive blood glucose out of the bloodstream, into our tissues, for use as immediate energy or stored energy (as fat or glycogen).

In diabetes and prediabetes, this function of insulin is impaired.

The tissues have lost some of their sensitivity to insulin’s action. This critical concept is called insulin resistance. Insulin still has some effect on the tissues, but not as much as it should. Different diabetics have different degrees of insulin resistance, and you can’t tell by just looking.  (There are several other hormones involved in regulation of blood sugar.)

Did you know that people who work at garbage dumps, sewage treatment plants, and cattle feedlots get used to the noxious fumes after a while? They aren’t bothered by them as much as they were at first. Their noses are less sensitive to the fumes. You could call it fume resistance. In the same fashion, cells exposed to high insulin levels over time become resistant to insulin.

Insulin resistance occurs in most cases of type 2 diabetes and prediabetes. So what causes the insulin resistance? It’s debatable. In many cases it’s related to overweight, physical inactivity, and genetics. A high-carbohydrate diet may contribute. A few cases are caused by drugs. Some cases are a mystery.

To overcome the body tissue’s resistance to insulin’s effect, the pancreas beta cells pump even more insulin into the bloodstream, a condition called hyperinsulinemia. Some scientists believe high insulin levels alone cause some of the damage associated with diabetes. Whereas a healthy person without diabetes needs about 50 units of insulin a day, an obese non-diabetic needs about twice that to keep blood sugars in check. Eventually, in those who develop diabetes or prediabetes, the pancreas can’t keep up with the demand for more insulin to overcome insulin resistance. The pancreas beta cells get exhausted and start to “burn out.” That’s when blood sugars start to rise and diabetes and prediabetes are easily diagnosed. So, insulin resistance and high insulin production have been going on for years before diagnosis. By the time of diagnosis, 50% of beta cell function is lost.

Steve Parker, M.D.

EXTRA  CREDIT  FOR  INQUISITIVE  MINDS

You’ve learned that insulin’s main action is to lower blood sugar by transporting it into the cells of various tissues. But that’s not all insulin does. It also 1) impairs breakdown of glycogen into glucose, 2) stimulates glycogen formation, 3) inhibits formation of new glucose molecules by the body, 4) promotes storage of triglycerides in fat cells (i.e., lipogenesis, fat accumulation), 5) promotes formation of fatty acids (triglyceride building blocks) by the liver, 6) inhibits breakdown of stored triglycerides, and 7) supports body protein production.

In his fascinating book, Cheating Destiny: Living With Diabetes, America’s Biggest Epidemic, James Hirsch describes what happened to type 1 diabetics before insulin injections were available. Type 1 diabetics produce no insulin. Until Frederick Banting and Charles Best isolated and injected insulin in the 1920s, type 1 diabetes was a death sentence characterized not only by high blood sugars, but also extreme weight loss as muscle and fat tissue wasted away. The tissue wasting reflects insulin actions No. 4, 5, 6, and 7 above.

Banting and Best worked at the University of Toronto in Canada. Their “discovery” of insulin is one of the greatest medical achievements of all time.

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Metabolic Improvements From a Paleolithic Diet in San Francisco

Posted on October 28, 2011 | 3 comments

A Paleolithic diet improved metabolic status with respect to cardiovascular and carbohydrate physiology, according to a 2009 study at the University of California San Francisco.

Here are the specific changes, all statistically significant unless otherwise noted:

  • total cholesterol decreased by 16%
  • LDL cholesterol (“bad cholesterol”) decreased by 22% (no change in HDL)
  • triglycerides decreased by 35%
  • strong trend toward reduced fasting insulin (P=0.07)
  • average diastolic blood pressure down by 3 mmHg (no change in systolic pressure)
  • improved insulin sensitivity and reduced insulin resistance; i.e., improved glucose tolerance

Methodology

This was a small, preliminary study: only 11 participants (six male, three female, all healthy (non-diabetic), average age 38, average BMI 28, sedentary, mixed Black/Caucasian/Asian).

Baseline diet characteristics were determined by dietitians, then all participants were placed on a paleo diet, starting with a 7-day ramp-up (increasing fiber and potassium gradually), then a 10-day paleo diet.

The paleo diet: meat, fish, poultry, eggs, fruits, vegetables, tree nuts, canola oil, mayonnaise, and honey.  No dairy legumes, cereals, grains, potatoes.  Alcohol not mentioned ever.  Caloric intake was adjusted to avoid weight change during the study, and participants were told to remain sedentary.  They ate one meal daily at the research center and were sent home with the other meals and snacks pre-packed.

Compared with baseline diets, the paleo diet reduced salt consumption by half while doubling potassium and magnesium intake.  Baseline diet macronutrient calories were 17% from protein, 44% carbohydrate, 38% fat.  Paleo diet macronutrients were 30% protein, 38% carb, 32% fat.  Fiber content wasn’t reported. 

I’m guessing there were no adverse effects.

Comments

This study sounds like fun, easy, basic science: “Hey, let’s do this and see what happens!”

I don’t know a lot about canola oil, but it’s considered one of the healthy oils by folks like Walter Willett.  It sounds more appealing than rapeseed, from whence it comes.

I agree with the investigators that this tiny preliminary study is promising; the paleo diet (aka Stone Age or caveman diet) has potential benefits for prevention and treatment for metabolic syndrome, diabetes, and cardiovascular disease such as heart attack and stroke.

The researchers mentioned their plans to study the paleo diet in patients with type 2 diabetes.  Any results yet?

Are you working with a physician on a medical issue that may improve or resolve with the paleo diet?  Most doctors don’t know much about the paleo diet yet.  You may convince yours to be open-minded by trying the diet yourself—not always a safe way to go—and showing her your improved clinical results.  Or show her studies such as this.

Steve Parker, M.D.

Disclaimer:  All matters regarding your health require supervision by a personal physician or other appropriate health professional familiar with your current health status.  Always consult your personal physician before making any dietary or exercise changes.

Reference:  Frassetto, L.A., et al.  Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet.  European Journal of Clinical Nutrition, advance online publication, February 11, 2009.   doi: 10.1038/ejcn.2009.4

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Posted in Glucose, Heart Disease, Insulin, Lipids, Paleo Diet

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