Metabolism and Aging

Intuitively, we all know that our metabolism slows as we age. Did you though this has been quantified? Here’s the chart of Basal Metabolic Rates in men and women vs age:

So this, at least in part, demonstrates why it is harder at 50 to lose weight than when we are 20. For a man of 20 their BMR is about 46 and the same man (at the same size) their BMR is around 38. That’s only 82% of the age at 20. So, yes, it is harder to lose weight since you have to eat less to lose weight than you did when you were young, but it is not at all impossible.

Even if you are older, you can do it.

 

What if the History of Diabetes Went Wrong?

In an interesting paper the question is asked what if the history of the development of our understanding of diabetes has it wrong? The paper (J. Denis McGarry. What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes. Science, Vol. 258, No. 5083 (Oct. 30, 1992), pp. 766-770).

Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistance
and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism.
Some powerful food for thought in the paper. Another paper (Arius, Energy Metabolism) summarizes the argument as:
The author considers the possibility that the hyperinsulinemia of early non-insulin—dependent diabetes is coincident with hyperamylinemia, since insulin and amylin are cosecreted. Amylin would cause an increase in plasma lactate (Cori cycle); and lactate, a better precursor than glucose for fatty acid synthesis, would indirectly promote the production of very-low-density lipoproteins (VLDL). There would follow an increased flux of triglycerides from liver to muscle (and adipose tissue) and, as proposed and elaborated on, an increase in insulin resistance and production of many of the metabolic disturbances occurring in diabetes.
 The author of the paper draws heavily on the Randle Cycle.
The Randle cycle is a biochemical mechanism involving the competition between glucose and fatty acids for their oxidation and uptake in muscle and adipose tissue. The cycle controls fuel selection and adapts the substrate supply and demand in normal tissues. This cycle adds a nutrient-mediated fine tuning on top of the more coarse hormonal control on fuel metabolism. This adaptation to nutrient availability applies to the interaction between adipose tissue and muscle. Hormones that control adipose tissue lipolysis affect circulating concentrations of fatty acids, these in turn control the fuel selection in muscle. Mechanisms involved in the Randle Cycle include allosteric control, reversible phosphorylation and the expression of key enzymes.[5] The energy balance from meals composed of differing macronutrient composition is identical, but the glucose and fat balances that contribute to the overall energy balance change reciprocally with meal composition.
Interesting thoughts.
Fatty acids may act directly upon the pancreatic β-cell to regulate glucose-stimulated insulin secretion. This effect is biphasic. Initially fatty acids potentiate the effects of glucose. After prolonged exposure to high fatty acid concentrations this changes to an inhibition.[13] Randle suggested that the term fatty acid syndrome would be appropriate to apply to the biochemical syndrome resulting from the high concentration of fatty acids and the relationship to abnormalities of carbohydrate metabolism, including starvation, diabetes and Cushing’s syndrome.
My own weight had been in the 280 range for a long time. In the months before I was diagnosed as Type 2 Diabetic my weight dropped 50 lbs without any lifestyle changes. After I went on Metformin my weight was relatively lower for a while. When I eventually went on Insulin my weight went up 40+ lbs fairly quickly. It is well known that Insulin adds weight.
My own thought is that the Insulin is both the lock and the key. Increased levels of Insulin pushes glucose or fat into cells and decreased levels of Insulin allows fat to come out of cells. That’s why Intermittent Fasting is such a great bullet for Type 2 diabetics. It allows our fasting Insulin levels to drop. Add to that Low Carbohydrate diets and the perfect recipe for controlling Diabetes comes into play.
The problem never really was Insufficient Insulin. The problem was too much Insulin. And clearly it is a fat related problem.

High Protein Diets are Good for Type 2 Diabetics

High Protein Diets are good at reducing NAFLD (Non-Alcoholic Fatty Liver Disease). From the study (February 2017, Volume 152, Issue 3, Pages 571–585.e8. Isocaloric Diets High in Animal or Plant Protein Reduce Liver Fat and Inflammation in Individuals With Type 2 Diabetes. Mariya Markova, Etc.):

In a prospective study of patients with type 2 diabetes, we found diets high in protein (either animal or plant) significantly reduced liver fat independently of body weight, and reduced markers of insulin resistance and hepatic necroinflammation. The diets appear to mediate these changes via lipolytic and lipogenic pathways in adipose tissue. Negative effects of BCAA or methionine were not detectable. FGF21 level appears to be a marker of metabolic improvement.

And from the conclusions section:

Postprandial levels of BCAAs and methionine were significantly higher in subjects on the AP vs the PP diet. The AP and PP diets each reduced liver fat by 36%−48% within 6 weeks (for AP diet P = .0002; for PP diet P = .001). These reductions were unrelated to change in body weight, but correlated with down-regulation of lipolysis and lipogenic indices. Serum level of FGF21 decreased by 50% in each group (for AP diet P < .0002; for PP diet P < .0002); decrease in FGF21 correlated with loss of hepatic fat. In gene expression analyses of adipose tissue, expression of the FGF21 receptor cofactor β-klotho was associated with reduced expression of genes encoding lipolytic and lipogenic proteins. In patients on each diet, levels of hepatic enzymes and markers of inflammation decreased, insulin sensitivity increased, and serum level of keratin 18 decreased.

 

Are you Insulin Resistant?

The original mission of this BLOG was to find a cure or at least a way of dealing with my own Insulin Resistance. A typical Type 2 Diabetic has Insulin Resistance.  I knew that was what it was called but what is Insulin Resistance and how can someone tell if they have Insulin Resistance?

This paper lays out one way to determine if you have Insulin Resistance (Ann Intern Med. 2003 Nov 18;139(10):802-9. Use of metabolic markers to identify overweight individuals who are insulin resistant. McLaughlin T1, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G.) using the numbers that you typically get when you get your blood work done.

Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).

To summarize (in US units):

  • Triglycerides > 130 mg/dL
  • Triglyceride to HDL ratio > 3.0 (using US units)
  • Insulin > 109 pmol/L

I haven’t ever had my Insulin measured so I don’t know what that number would be but I did have the other numbers done in 2015 and here are my numbers:

  • Triglycerides = 460 mg/dL
  • HDL Cholesterol = 36
  • Ratio = 12.7

Those numbers are well over the numbers that trigger the diagnosis of Insulin Resistance (aka Metabolic Syndrome). Check your own numbers to see where you are.

 

Another Protein Experiment

I did a previous Protein Experiment where I compared the response of my Blood Sugar to 50 grams of Whey Protein vs 50 grams of Casein Protein. Since both of those were “pure” Protein with very little fat, I was curious how those results would compare to animal protein which had fat.

For this experiment I chose Chicken Drumsticks. I weighed them amount of mean (total minus bones left at the end) and the nutritional information shows them to have been close to 50g of Protein:

Here is the Blood Glucose numbers (smoothed) over several hours added to the data from the original Whey/Casein test.  The chicken drumsticks are in yellow.

Accounting for Differences

  1. The drumsticks (in yellow) are lower overall because I have been on the PSMF longer and my blood sugar levels have dropped. This is evidence, at least to me, that the PSMF is doing good things for my metabolic health.
  2. There was a dip at the start of the chicken wing experiment which was due to exercise. In this case it was a particularly grueling Saturday morning routine with a lot of lifting and burpees, etc.  That explains the drop from 72 down to 64 at the start.
  3. The highest number was very comparable to the Whey and Casein numbers in terms of rise from the minimum. The max rise in Blood Sugar in all of these cases was no more than 20 units.
  4. The slope down with the animal Protein is longer and slower. That may explain less feelings of hunger as the consumption of the Protein ends.
  5. The curve is longer than either of the “pure” Proteins. The fat may extend that longer than the pure proteins. I’d like to repeat the experiment with low fat chicken breasts and see if it’s the fat or if it is the animal Protein vs Milk Protein of the Whey/Casein choices that makes a difference.

Conclusions

50 grams of Protein is a decent serving size. It is more than enough to stimulate Protein Muscle Synthesis.

All in all, I see nothing to worry about with eating Protein even for Type 2 Diabetics like myself. With all of the “Protein turns into candy bars” fear mongering out there, some sanity needs to be applied to the subject.

Disclaimer

Of course, I would encourage any diabetic to test to see where they are with this same test. At least this way they know what effect Protein would have on their body. If they are a Type 1 Diabetic this information could be helpful to determine what amount of Insulin they should add for Protein.

 

Explanations for Blood Sugar Rise with Protein Consumption

 

Here’s my questions/comments for the KetoGains thread on this subject.

I’ve been trying for a while to wrap my head around this subject. Here’s what I think at the moment. Would welcome any feedback on where I am missing it.

1 – My blood sugar meter shows that my blood sugar goes up 25 points with Protein (50g of whey) for a couple of hours. Not a bad increase since it’s only from 85 to 110 (US units). I have documented this at: http://land-boards.com/T2D/2017/09/26/blood-sugar-response-to-proteins/ .

2 – My blood sugar drops fairly rapidly at the end of the two hours (makes me hungry) which decreases when the blood sugar levels out. As long as I keep that in mind and keep food out of reach in that time frame I am OK. Otherwise, it seems like my body is telling me that it wants is ready to eat more Protein (or just food).
3 – Blood sugar production proceeds at a constant rate which isn’t all that much affected by Protein consumption. I’ve seen enough studies to believe that is probably the case such as //diabetes.diabetesjournals.org/content/62/5/1435. Also, the demand vs supply GNG argument seems strong. This rules out the idea of GNG being increased by the Protein.
4 – In a non-diabetic blood sugar doesn’t rise as much with ingested Protein as it does in a T2 Diabetic. It may not raise at all. I plan on an experiment with a “healthy” friend to confirm this for myself although the studies say it is “minimal”. But is that difference due to broken Insulin Resistance in the T2 Diabetic? As the Insulin goes up to deal with the Protein does that increase the Insulin Resistance of the cells at the same time and block the glucose from being consumed?
5 – The failure for a T2 Diabetic seems to be able to reduce the production of glucose in response to consumption of Protein (or one of the downstream aspects of the consumption). The Glucose (argued above) is getting “backed up” in the process and not being disposed by Insulin since the Insulin is “busy” dealing with the Amino Acids (all in all a very good use of Insulin).

So although arguably Protein doesn’t turn into glucose directly since Protein does lead to a rise in Blood Sugar (in T2 Diabetics) then what difference does it make if it is increased levels of GNG or an inability to reduce the rate of GNG or due to Insulin Resistance? Either way, the result is the same, Blood Sugar goes up (for T2 Diabetics) with protein consumption.

So then the question for me is whether or not Blood Sugar going up by a relatively small amount in a keto dieter who is eating lots of Protein actually a problem? Normally, us diabetics are trained to do things to minimize their blood sugars. This notion is leading a lot of people to eat a lot of fat and less Protein than they probably should.

Put another way, does the advantage of eating more Protein (maintain or growing Lean Body Mass among others) outweigh the disadvantage (marginally higher blood sugars for short periods of time)?

Survey of the Scientific Literature

From an 20 year old article (Diabetes Educ. 1997 Nov-Dec;23(6):643-6, 648, 650-1. Protein: metabolism and effect on blood glucose levels. Franz MJ):

Insulin is required for carbohydrate, fat, and protein to be metabolized. … Protein has a minimal effect on blood glucose levels with adequate insulin. However, with insulin deficiency, gluconeogenesis proceeds rapidly and contributes to an elevated blood glucose level. With adequate insulin, the blood glucose response in persons with diabetes would be expected to be similar to the blood glucose response in persons without diabetes. The reason why protein does not increase blood glucose levels (sic: in a non-diabetic) is unclear. Several possibilities might explain the response: a slow conversion of protein to glucose, less protein being converted to glucose and released than previously thought, glucose from protein being incorporated into hepatic glycogen stores but not increasing the rate of hepatic glucose release, or because the process of gluconeogenesis from protein occurs over a period of hours and glucose can be disposed of if presented for utilization slowly and evenly over a long time period.

Questions raised by this article:

  1. They don’t define “minimum effect” so is a 20 point rise considered to be a “minimum effect”?
  2. Another study indicates that GNG is much more efficient in a Diabetic. Is that because of an Insulin deficiency (the way it is worded above)? Or is that due more to Insulin Resistance?

Here’s a curve from one paper which shows the body’s Insulin response to Protein vs Carbohydrates which shows that the body has a similar response to Protein as it does to Carbohydrates when it comes to Insulin Levels:

This seems to be a reasonable study (Claire Fromentin1,2, Daniel Tomé1,2, Françoise Nau3, Laurent Flet4, Catherine Luengo1,2, Dalila Azzout-Marniche1,2, Pascal Sanders5, Gilles Fromentin1,2 and Claire Gaudichon1,2. Dietary Proteins Contribute Little to Glucose Production, Even Under Optimal Gluconeogenic Conditions in Healthy Humans. Diabetes 2013 May; 62(5): 1435-1442.) which concludes:

We showed that after a normal intake of protein (20–25 g), the contribution of dietary protein to glucose production was small and did not exceed 10% of the total flux during the 8-h postprandial period, contributing the production of 4 g glucose to 50 g of total glucose production.

While that is true in healthy humans (the subject of this study), is it also true of Diabetic persons?

From one of the comments in this thread

Higher protein intake, which needs insulin response to get it where it needs to be, will increase physiological insulin resistance (adaptive glucose sparing) in order to get the protein into where it needs to go without pushing more glucose into the cells. this will result in seeing a higher fasting blood glucose, and lower circulating ketones, as they replace glucose as a fuel for the tissues that previously used more of it.

Here’s the pieces of the puzzle.

  • Body produces a relatively constant level of blood sugar
  • Non diabetics have little to no rise in Blood Sugar when they eat Protein
  • In a diabetic the down regulation of blood sugar in the presence of Insulin is faulty
    1. Eat Protein
    2. Body begins digesting Protein
    3. Pancreas increases Insulin production to push protein into muscle cells
    4. As Insulin goes up so does Insulin Resistance of the muscle cells to Glucose (difference between a diabetic and a non-diabetic)
    5. Because Glucose is not being disposed by the muscle cells as well, the level of Blood Sugar rises temporarily
    6. After the Protein is processed by the body the Blood Glucose drops

So the theory here is that while the blood sugar rises over the short term it is not being pushed into the cells.

 

Electrolytes, Water Retention, Low Carb Diets

Low Carb Diets reduce the Insulin load on the body. They are also known for requiring more electrolytes. Here’s a study that shows that salt levels are directly impacted by Insulin levels (J Clin Invest. 1975 Apr; 55(4): 845–855. The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. R A DeFronzo, C R Cooke, R Andres, G R Faloona, and P J Davis).

Another related subject (Metabolism. 2011 Jul;60(7):965-8. doi: 10.1016/j.metabol.2010.09.005. Epub 2010 Oct 30. Low-salt diet increases insulin resistance in healthy subjects. Garg R1, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK.)

Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR.

Carbs get worse with every study

Check out the conclusion from this study (Meenakshi Ravichandran, Gerald Grandl, Michael Ristow; Dietary Carbohydrates Impair Healthspan and Promote Mortality; Cell Metabolism, Volume 26, Issue 4, p585–587, 3 October 2017):

Taking the body of preceding evidence both from model organisms as well as human epidemiology into account, we therefore believe that current nutritional recommendations in regards to macronutrients, but most importantly in regards to refined carbs and sugar, should indeed be fundamentally reconsidered.

This was no small study. And it had a neat chart.

Is Type 2 Diabetes a disorder of Insulin, Glucose or Glucagon ?

The popular notion is that Diabetes is too much glucose in the blood. Hence, treatment is given to reduce the production of blood sugar. Hence a low carbohydrate diet is given as the solution since it removes the substrate for glucose.

Dr Fung and others present the insight that the problem is that there is too much Insulin present. Type 2 Diabetics usually produce a normal level of Insulin but their blood sugars are so high that they can’t produce enough Insulin. (Type 1 is someone who just can’t produce Insulin). Low Carb works with this since it reduces the demand for Insulin to combat higher glucose levels.

There’s another player that may be more important than either Glucose or Insulin. That’s Glucagon. Hyperlipid BLOG has an article on the subject. The key insight is:

Eating 75g of casein protein more or less triples your blood insulin level but doesn’t budge blood glucose down any more than cream does, which leaves insulin pretty well alone.

The author links (Unger RH1, Cherrington AD.; Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover; J Clin Invest. 2012 Jan;122(1):4-12. doi: 10.1172/JCI60016. Epub 2012 Jan 3).

Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes. We base this on the following evidence: (a) glucagon increases hepatic glucose and ketone production, catabolic features present in insulin deficiency; (b) hyperglucagonemia is present in every form of poorly controlled diabetes; (c) the glucagon suppressors leptin and somatostatin suppress all catabolic manifestations of diabetes during total insulin deficiency; (d) total β cell destruction in glucagon receptor-null mice does not cause diabetes; and (e) perfusion of normal pancreas with anti-insulin serum causes marked hyperglucagonemia. From this and other evidence, we conclude that glucose-responsive β cells normally regulate juxtaposed α cells and that without intraislet insulin, unregulated α cells hypersecrete glucagon, which directly causes the symptoms of diabetes. This indicates that glucagon suppression or inactivation may provide therapeutic advantages over insulin monotherapy.

Here’s another paper with the same premise (Lee YH, Wang MY, Yu XX, Unger RH.; Glucagon is the key factor in the development of diabetes; Diabetologia. 2016 Jul;59(7):1372-5. doi: 10.1007/s00125-016-3965-9. Epub 2016 Apr 26.).

 

Potato Diet Guy

There’s a news story from 2016 about a guy down under who ate nothing but potatoes for an entire year. He lost a bunch of weight. People use it as “proof” that you don’t need to be on a Low Carb diet to lose weight. Let’s look at his diet (ignoring the monotony of only eating spuds).

  • Starting weight: 151.7kg (333.7 lbs)
  • Weight loss: 110 lbs
  • Food Consumed per day: “three kilograms of potatoes”

There’s no indication whether or not he ate the 3kg (6.6 lbs) of potatoes every day or whether that was an average or whether that was what he ate earlier in the diet and it then decreased. But let’s assume he ate the potatoes throughout the diet at the same rate although it would probably be safe to assume the amount of potatoes dropped over time.

Potato Nutritional Facts

The nutritional facts for 100g of potatoes are:

Three kg of potatoes would be 30x as much as the 100g serving above. So what he was eating for macros were:

  • Carbs 17g (minus 2.2g for fiber is net 14.8g) x 30 servings/day =  444g per day or 1776 cals. Higher than the Standard American Diet but without the problematic fat-carb mix that most people eat.
  • He was getting the protective effects of 2.2g of fiber per serving x 30 servings or 66g of fiber a day. Fiber has a protective effect against carbs acting as a buffer.
  • His protein was 66g a day which isn’t too low. Potatoes have a complete protein in them (If All You Ate Were Potatoes, You’d Get All Your Amino Acids). There’s also nothing in the articles which indicate any changes to his Lean Body Mass. Still, probably marginally OK protein levels from his diet.
  • And he was only eating 0.1 x 30 = 3g of fat a day. Not a problem given his high level of body fat.

His calorie consumption would have been 77 x 30 = 2310 calories per day. His caloric needs would have been around 4000 calories per day at the start. At a 1700 calorie a day deficit he could drop 1/2 lb of body fat every day – at least at the start. He had more that enough body fat to meet the deficit although it may have gotten more difficult near the end when he was down to 217 lbs.

Nothing miraculous in all of that. He did cut out all processed foods which are the core problem for many people causing inflammation, etc. There’s no indication he was a diabetic or had any blood sugar issues from the high level of carbohydrates so he’s not a great example since many people have Metabolic Syndrome.

Just to be clear, there’s no way I am recommending his diet to anyone who isn’t more than 100 lbs overweight, had no symptoms of metabolic syndrome, etc.