The RCT That Will Never Happen

Here’s the Randomized Control Trial that I really want to see.

Take a lot of Type 2 Diabetics with BMIs in the obese range. Split them into two groups who are pair matched. Start one of the groups on Low Carb / High Fat diet and leave the control group on their customary Standard American Diet (SAD). Treat all of them with the standard of care as it is at the time. Track them for 40 years and look at the outcomes. Don’t just track some of the benchmarks like LDL cholesterol. Track all of their results including all-cause mortality. 

It won’t happen for too many reasons. And it doesn’t take a belief in conspiracy theories to figure out why. Perhaps the biggest reason is nobody makes money with Low Carb/High Fat and a study with sufficient statistical power would be very expensive.

In the meanwhile, we are all n=1. And none of us have 40 years. And no point in looking for the RCT above since it’s never going to happen. It would have had to start before anyone knew the right questions to ask.

How Low to Go?

I’ve done somewhere around 50 grams of carbohydrates a day (30 grams when subtracting out fiber) for the past year. And my blood sugar control has been great. I’ve wondered how low someone has to go (or stay) in order to control Type 2 Diabetes. Certainly, the weight loss I’ve had (120 lbs) is a part of the solution. Being at a low body fat percentage now (7.5% per BodPod) has to help as well. My weight has been stable for 6 months now as well which means I’ve not lost or gained any weight – I was at 164.7 lbs when I took the BodPod test and today I weighed 163.7 lbs (close enough). My coffee consumption (which helps in weight loss for sure) is higher than ever before but I’m trying to keep the caffeine down by mixing in mostly decaf coffee. 

So all of this begs the question of how many grams of carbs I could tolerate. Now, I am not going to be testing this anytime soon. I find the advantages of being low carb just way too easy (see above for the results). I did find a study that might provide at least a partial answer to the question of how many grams of carbs can keep someone in remission from Diabetes.

The answer is in this 2009 study (Haimoto H, Sasakabe T, Wakai K, Umegaki H. Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes. Nutr Metab (Lond). 2009 May 6;6:21).

Now, I wouldn’t even call this diet at 30% of calories from carbohydrates a “Low Carbohydrate” by any definition that I would recognize but it has interesting results. One of the things that was interesting is that the study was done on severe diabetics (HbA1c levels of 9.0% or above). This is not a group of new diabetics nor were the participants young. They were a pretty good representative of Type 2 Diabetics with poor blood sugar control. The participants:

were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs.

The results were really good. Many of the participants got off their medications and:

HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months.

These are similar to the results I got with the Low Carbohydrate diet when I got to an HbA1c level of 6.4. They are not as good as the results I got over the last couple of years with even lower levels of carbohydrates plus intermittent fasting.

In spite of being on a fairly low calorie diet (1852 kcal) they didn’t lose much weight. This group also didn’t seem to be all that obese since their BMI was around 24 (top end of “normal” weight).

Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6months (23.5 ± 3.4).

So, if you are “normal” weight and diagnosed as diabetic then dropping from the Standard American Diet (SAD) 50% of calories from carbohydrates to 30% might give as good of control as exogenous Insulin without the long term increase in insulin resistance that comes along with Insulin therapy.

There was one telling outlier in the data.

One female patient had an increased physical activity level during the study period in spite of our instructions. However, her increase in physical activity was no more than one hour of walking per day, four days a week. She had implemented an 11%-carbohydrate diet without any anti-diabetic drug, and her HbA1c level decreased from 14.4% at baseline to 6.1% after 3 months and had been maintained at 5.5% after 6 months.

Insulin Glucagon Glucose

Here’s a fun watch that is of interest to diabetics. And nerds.

On the Hyperlipid BLOG (Insulin glucagon and protein) examined this study (Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover. J Clin Invest. 2012 Jan;122(1):4-12). The study looked at Diabetes as a disorder more related to glucagon than insulin. In particular, the Hyperlipid BLOG considered the blood sugar response of a diabetic to protein. I did the same thing myself here in this BLOG several times (Glucose Response to ProteinBlood Sugar Response to Proteins and Blood Sugar Responses Compared).

The paper presents the following lines of evidence for the claim,

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.

The insight that this may not be as much an insulin issue as a glucagon issue is a powerful one which may have application with medications to control Type 2 Diabetes. If giving exogenous insulin produces problems with Insulin Resistance, giving a medication which causes the body to produce less glucagon may have an opposite effect. It may be possible to develop a medication which downregulates glucagon indefinitely.

This has been tried in a 2017 Phase I drug study (Glucagon-Blocking Drug Reduces Need for Insulin and Improves Blood Glucose Levels for Patients with Type 1 Diabetes). Here is the full paper for the study (Effect of a glucagon receptor antibody (Jeremy Pettus MD. REMD‐477) in type 1 diabetes: A randomized controlled trial).

What is the cost (in other systems in the body) if glucagon is downregulated? 

Is eating 50g of Whey Protein a good replacement for the OGTT? I think it’s a much better choice than eating 75g of glucose.

Am I Still a Diabetic?

That’s a challenging question since by most tests I am not a diabetic. I no longer take diabetic meds and have good control of my blood sugars. The Type 2 Diabetes ADA Diagnosis Criteria are any of the following:

  1. A hemoglobin A1c (HbA1c) level of 6.5% or higher; the test should be performed in a laboratory using a method that is certified by the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay, or
  2. A fasting plasma glucose (FPG) level of 126 mg/dL (7 mmol/L) or higher; fasting is defined as no caloric intake for at least 8 hours, or
  3. A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or
  4. A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia (ie, polyuria, polydipsia, polyphagia, weight loss) or hyperglycemic crisis

I have changed the bullet-ted list to a numbered list for convenience. I am on no diabetes medications to mask the results here:

  1. My last HbA1C was 5.2 so I pass this test.
  2. My fasting plasma glucose is less than 100 typically so I pass this test.
  3. I have not had an OGTT (more on this to follow).
  4. I have none of the symptoms of hyperglycemia at all and I have had no blood sugar measurements of 200 or higher (or anywhere near that level) since I started Low Carb.

Oral Glucose Tolerance Test (OGTT)

I don’t know if I would pass an OGTT or not. I assume I would fail such at test in spite of losing 120 lbs, etc. The reason I assume I would fail is that I think part of being on a Low Carb ketogenic diet is that my body has developed peripheral insulin resistance.

Peripheral Insulin Resistance

PIR is a normal response to the ketogenic diet and happens as a response to lowered glucose availability. Here’s a mouse study which shows that Peripheral Insulin Resistance got worse under a ketogenic diet (Kinzig KP, Honors MA, Hargrave SL. Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology. 2010;151(7): 3105-14.). The study measured:

After 8 wk of consuming chow or KD, caloric intake after peripheral or central insulin and insulin and glucose levels after a glucose challenge were assessed. In a separate group of rats, glucose and insulin responses to either a low- or high-carbohydrate test meal were measured. Finally, rats maintained on KD were switched back to a chow diet, and insulin sensitivity and glucose tolerance were evaluated to determine whether the effects of KD were reversible.

That answers the test that I would want to do to determine if I would pass an OGTT. What happened to the mice?

Maintenance on KD resulted in decreased sensitivity to peripheral insulin and impaired glucose tolerance.

So after 8 weeks of not eating carbohydrates the mice had trouble eating carbohydrates. Not much of a surprise there. It would take a deeper dive to see how much worse their PIR and IGT became.

Furthermore, consumption of a high-carbohydrate meal in rats that habitually consumed KD induced significantly greater insulin and glucose levels for an extended period of time, as compared with chow-fed controls.

So the mice over-reacted to carbohydrate meals by producing more glucose and insulin.

Responsivity to central insulin was heightened in KD rats and associated with increased expression levels of insulin receptor mRNA.

Not sure how to understand that if the mice were more insulin resistant. But was this effect a permanent change or was it temporary and a side effect of the diet itself?

Finally, returning to a chow diet rapidly reversed the effects of KD on insulin sensitivity and glucose tolerance. These data suggest that maintenance on KD negatively affects glucose homeostasis, an effect that is rapidly reversed upon cessation of the diet.

Although 8 weeks isn’t that long to a human it’s a long time to a mouse. I don’t know the scaling factor but it’s reasonable to assume it is years rather than the two months of the study.

So, if someone is concerned about whether or not they would pass an OGTT it seems like they probably could stop the ketogenic diet for some time (weeks maybe?) and then take the test. Most of us who do LC / Keto won’t be trying it anytime soon.

The fact is your doctor is not going to order an OGTT for you if you don’t fail one or more of the other numbers. In fact, if you fail the fasting blood sugar test the doctor might order you an HbA1C test for confirmation. And then, depending on other factors, may just decide to keep an eye on it.

How Metformin Works

Researchers have unlocked more about how Metformin works (
Zydrune Polianskyte-Prause, Tuomas A. Tolvanen, Sonja Lindfors, Vincent Dumont, Mervi Van, Hong Wang, Surjya N. Dash, Mika Berg, Jette-Britt Naams, Laura C. Hautala, Harry Nisen, Tuomas Mirtti, Per-Henrik Groop, Kristiina Wähälä, Jukka Tienari, and Sanna Lehtonen. Metformin increases glucose uptake and acts renoprotectively by reducing SHIP2 activity. The FASEB Journal 0 0:0. 15 Oct 2018).

Metformin inhibits SHIP2 in cultured cells and in skeletal muscle and kidney of db/db mice. In SHIP2-overexpressing myotubes, metformin ameliorates reduced glucose uptake by slowing down glucose transporter 4 endocytosis. SHIP2 overexpression reduces Akt activity and enhances podocyte apoptosis, and both are restored to normal levels by metformin. SHIP2 activity is elevated in glomeruli of patients with T2D receiving nonmetformin medication, but not in patients receiving metformin, compared with people without diabetes. Furthermore, podocyte loss in kidneys of metformin-treated T2D patients is reduced compared with patients receiving nonmetformin medication.

So not only does Metformin reduce the glucose production of the liver by downregulating GNG (Joseph A. Baur and Morris J. Birnbaum, Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo.Nature Medicinevolume 24, pages1384–1394 (2018)), it also increases the uptake of glucose in skeletal muscle and the kidneys.

Another paper on the action of Metformin (Baur JA, Birnbaum MJ. Control of gluconeogenesis by metformin: does redox trump energy charge?. Cell Metab. 2014;20(2):197-9.).

Here’s yet another paper on an effect of Metformin (Cheryl A. Collier, Clinton R. Bruce, Angela C. Smith, Gary Lopaschuk, and David J. Dyck. Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle).

Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity.

High Blood Sugar Without Side Effects?

There’s a small set of people who have a genetic defect (GCK-MODY) which gives them high blood sugar levels but they have no diabetic side effects. This paper looks at this group (Ali J. Chakera, Anna M. Steele, Anna L. Gloyn, Maggie H. Shepherd, Beverley Shields, Sian Ellard, Andrew T. Hattersley. Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation. Diabetes Care Jul 2015, 38 (7) 1383-1392).

Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population.

They don’t treat these people since they don’t respond to medications.

Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications.

These people don’t get extra high levels of blood sugar but they are in the range diagnosed for pre-diabetic up to diabetic.

People with GCK-MODY have an HbA1c between 5.8 and 7.6%.

It seems to me that this might be evidence of something other than the blood sugar being the cause of damage in diabetics. Could it be the higher Insulin levels (hyperinsulinemia)? The paper presents some possibilities.

This is likely to be due to a number of factors: the hyperglycemia is mild, stable, and under homeostatic regulation; the hyperglycemia is often lower than the threshold above which the risk of diabetes complications increases; and people with GCK-MODY do not have the additional burden of the metabolic syndrome, with weight, lipid profile, and blood pressure being comparable with the general population 

Low Carb Diet and Type 1 Diabetics

Part 2 takes a look at newer studies.

Here’s a 2018 systematic review  which looked at Type 1 Diabetics and the Low Carb Diet (Jessica L. Turton, Ron Raab, Kieron B. Rooney. Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. PLoS ONE 13(3): e0194987). They looked through a lot of studies and narrowed down to:

A total of nine studies were eligible and included for this review.

The nine studies were:

two randomised controlled trials , four pre-post intervention studies two retrospective case-series, and one case-report.

There was considerable differences between the nine studies:

Results for our primary outcome (HbA1c) were available from eight of nine studies reviewed. Results for secondary outcomes of interest were inconsistently reported. Two studies reported the effect of a low-carbohydrate diet on frequency of severe hypoglycaemia, five studies reported total daily insulin, three studies reported BMI, and one study reported mean daily blood glucose.

Here’s the detailed data (click to see large image).

The results were disappointing for HbA1C.

Four studies reported non-significant changes in HbA1c with a low-carbohydrate diet and three studies reported statistically significant reductions (P < 0.05).


Of the five studies that reported daily insulin usage, two TLCD studies  demonstrated statistically significant reductions in total daily insulin within carbohydrate restriction groups (P < 0.05) with one study also reporting a statistically significant difference between the low-carbohydrate group and high-carbohydrate comparator (P < 0.05). Levels of significance could not be calculated or obtained in three studies due to inadequate sample size and lack of raw participant data.

The reduction in Insulin use is important since that could forestall Insulin Resistance in the Type 1 diabetic. It’s a serious problem when the Type 1 Diabetic becomes resistant to the very medication that they need to live. As the paper put it:

The excessive use of insulin that is often required to achieve glycaemic control in type 1 diabetes increases susceptibility to severe hypoglycaemia and may lead to some measure of hyperinsulinemia. Hyperinsulinemia is associated with; excessive weight gain, development of the metabolic syndrome, inflammation and atherosclerosis, Alzheimer’s Disease and cancer. Findings of the present review suggest that low-carbohydrate intakes may assist in reducing or preventing hyperinsulinemia in type 1 diabetes by decreasing the absolute amount of insulin required for tight glycaemic control.

The conclusion of the study was:

This systematic review presents all available evidence for low-carbohydrate diets in the management of type 1 diabetes mellitus. The existing body of evidence is limited and more primary studies evaluating the short and long-term effects of low-carbohydrate diets on type 1 diabetes management outcomes are necessary to support its use in practice.



Long Term Adherence to Low Carb for Diabetics?

I don’t personally find long term adherence to a low carb diet to be difficult. It will be two years next month for me on Low Carb. The rewards outweigh any desire to change away from the low carb diet. In fact, the only pressure has been to maintain my weight on Low Carb since I keep losing. I never thought I would weight 165 lbs and I’ve been in this range for months.

But, there is evidence that many people who are in trials are less motivated to keep the benefits of the low carb diet past a year. Here’s a study which makes that point (Ole Snorgaard, Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2017; 5(1): e000354.).

We identified 10 randomized trials comprising 1376 participants in total. In the first year of intervention, LCD was followed by a 0.34% lower HbA1c (3.7 mmol/mol) compared with HCD (95% CI 0.06 (0.7 mmol/mol), 0.63 (6.9 mmol/mol)).

The greater the carbohydrate restriction, the greater the glucose-lowering effect (R=−0.85, p<0.01).

At 1 year or later, however, HbA1c was similar in the 2 diet groups.

The effect of the 2 types of diet on BMI/body weight, LDL cholesterol, QoL, and attrition rate was similar throughout interventions.

Does Low Carb Itself Only Work for a Year?

There’s nothing about the Low Carb diet itself which means that if you follow the Low Carb diet for a year the benefits end. My own HbA1C before Low Carb ranged from around 7-9 and now it is 5.2 at 18 months after I started Low Carb. Low Carb didn’t stop for me at a year.

My 90 day average blood sugar is 92 per my meter.

“Diet is Temporary”

Rather, it is lack of long term adherence to the diet which is the problem. If a diabetic thinks that they can do Low Carb and all their problems will go away without any potential for re-occurrence they are missing the point of how they got messed up to start with. Re-introduce a high carb load and the diabetic symptoms will quickly return.

Transition to Maintenance

People take the advice that they should increase their carbohydrates once the intervention ends and they just can’t do that. The Low Carb diet has to be followed for as long as a person wants to be non-diabetic. The transition strategy to higher carbs needs to be “just say no” rather than “try and find your carb tolerance”.

Motivated by a Study

On some level this is a problem with the nature of a study since the participants have a different set of motivations than someone who undertakes a Low Carb diet by their own choice. People who do a study are motivated by the study. A diabetic who finds low carb and reverses their diabetes has an entirely different motivation.

Study Participants

Many times these studies are very selective in the population they are studying.  Inclusion criteria is often to be newly diagnosed and un-medicated. That’s a less motivated crowd. They often have no serious symptoms (at least that they can see) and are less motivated to stay non-diabetic.

Study participants are rewarded for participating in studies not long term adherence. Once the study is over their motivation ends.

Too Easy to Pop a Pill

At the start of diabetes it is really simple to just pop a pill. And the HbA1c will react quite nicely to the pill. At least for a while.

What they don’t tell you is that you will eventually be on Insulin. I used to be in a small Bible study group with older men. There were around 6-8 of us and all of us except once guy were Type 2 diabetics. We all shared the same trajectory. We all started with Metformin which worked for a couple of years. Then our blood sugar numbers got worse. And we were prescribed additional oral medications. Eventually, we were all put on Insulin. Once of the guys commented one day that they never tell you when they put you on Metformin that it would eventually result in you getting put on Metform.

One Significant Takeaway

It seems obvious to me but the study found that the greater the carbohydrate restriction the greater the reduction in HbA1c value. This is worth noting all by itself. Here’s the figure from the study:


The cross over point is somewhere around 40% of energy. Assuming a 2000 calorie diet that’s 800 calories or 200 grams of carbohydrates. Above that point things get worse.

Equally the maximum benefit of around 0.8% reduction in HbA1c was found at 15% of energy from carbs. Again assuming a 2000 calorie diet that’s 300 calories or 75 grams of carbohydrates. That’s still high by my own standards.


Curing Diabetes

I wrote the following to respond to a post about Jason Fung on Carb Sane (Diabetes Un-Funged). Her central thesis is that exogenous Insulin doesn’t cause Insulin Resistance.

I was a T2DM for 13 years (and probably undiagnosed for 8 years before that).

Two years ago, I went from 100 units a day of Insulin (Medtronics Pump) to zero in two weeks following Fung’s methods (Low Carb and Intermittent Fasting) with great blood sugar levels. I did Low Carb in the past and it helped me get a decent HbA1C but not out of the diabetic range. Fast forward 22 months and I am down 120 lbs (current weight is 165). My HbA1C was 5.2 a few months ago. No longer on HBP meds (I was on them for 20 + years). All of this while following Fung’s methods (Low Carb and Intermittent Fasting).

As to the progression of Insulin and loss of blood sugar control points in your article. In my own case I went from 40 units of Insulin with good control to 100 units with poorer control (higher HbA1C) in 4.5 years. The more I tried to control my blood sugar with Insulin the higher the amount of Insulin I required kept getting.

Worse yet the real surrogate of Insulin Resistance is the ratio of grams of carbs to units of Insulin. Anyone who has been on Insulin for a long time can testify that this ratio degrades with time. At the start, 1 unit of Insulin would cover 15 grams of carbohydrates and 4.5 years later one unit would only cover 4 grams of carbs. Clearly (at least to me) this is evidence of progressive insulin resistance).

Even if you don’t agree with Fung’s reasons his method is essentially the same as yours (Low Carb). Problem for me was that without having an intermittent fasting window I would have just had lower Insulin requirements – not a cure, but a decent treatment. I got to HbA1C of 6.6 with Low Carb and Insulin.

And it wasn’t about weight loss since most of what someone loses in the first week or two is water weight. I think it was more about leaning out the liver and then leaning out the fat around the pancreas than anything else…

Incidentally, this wasn’t about titrating the dosage of Insulin over the four and a half years. The “honeymoon period” is well known among people who start using diabetes meds – including Insulin. It isn’t long until more is required as the body becomes more resistant to the insulin.

Another line of evidence is the studies showing that hyperinsulinemia precedes diabetes and obesity often by decades.

How Type 2 Diabetics Gain Weight on Insulin

This study looks at how a Diabetic is affected strongly by taking Insulin (A. Franssila-Kallunki, L. Groop. Factors associated with basal metabolic rate in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia; October 1992, Volume 35, Issue 10, pp 962–966.). The study looked at:

66 Type 2 (non-insulin-dependent) diabetic and 24 healthy age- and weight-matched control subjects…

The interesting part is that some of the diabetics were looked at both before and after insulin therapy.

Eight Type 2 diabetic patients were re-studied after a period of insulin therapy.

In the following analysis, take note that the group put on Insulin therapy was a subset of the original group of Diabetics so their numbers were different (more exaggerated) from the rest of the Diabetics group.

Weight Gain on Insulin

The group on the Insulin treatment saw their BMI increase from 28.2 to 29.6 kg/m^2.

Basal Metabolic Rate

The control and Diabetics groups were weight matched. Surprisingly, the BMR in the Diabetics was 13% higher than the control group:

Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 ± 1.9 J · kg LBM−1-min−1 vs 90.7 ± 2.8 J · kg LBM−1;min−1; p<0.01)

Insulin treatment reduced the BMR of the Diabetics (115.5 ± 5.6 to 103.1 ± 5.7). It is question begging whether the lowered BMR caused the BMI increase with Insulin.

Diabetics Produce More Glucose

Not surprisingly the Type 2 Diabetics were producing glucose from their livers at significantly higher rates than the control group.

 The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 ± 29.9 vs 789.3 ± 41.7 μmol/min; p <0.001)

Insulin therapy decreased glucose production (1133 ± 92 to 983 ± 80). In theory this is good. A possible explanation of the effect of Insulin is that it took more insulin to overcome the Insulin Resistance of the liver. Insulin therapy isn’t a great long term solution, though, since the liver will eventually become even more Insulin Resistant and require ever increasing levels of exogenous Insulin.

Insulin Therapy Reduced Fat Oxidation Rate

The fat oxidation of the Diabetics was reduced when Insulin therapy was added:

Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 ± 0.05 vs 1.37 ± 0.08 μmol · kg LBM−1 · min−1‘; p <0.01) and decreased significantly after insulin therapy (p<0.05).

The lipid oxidation rate fell from 2.1 ± 0.1 to 1.4 ± 0.1 with the addition of Insulin therapy. A key phrase in the discussion section is:

lipid oxidation accounted for the major part of the BMR

So, putting someone on Insulin reduces their fat oxidation rate. If Type 2 Diabetes is a problem of fat build-up then Insulin therapy isn’t helping. It’s making Diabetics fatter. Yes, it is driving down Serum Glucose levels in the short term.

Fasting Insulin

Of note is the difference in the Fasting Serum Insulin levels between the Diabetics (64 ± 5) and the control group (37 ± 4).

The subset of the Diabetics put on Insulin therapy had higher Fasting Insulin levels than the lumped group of all diabetics. With the addition of exogenous Insulin therapy the Fasting Serum Insulin levels in the Diabetic (subset) increased from 84 to 132.

That would, of course, indicate that the part of the Diabetics group that was not put on Insulin had a much lower fasting Insulin level. This is interesting given that the error bar was ±5 so the group put on Insulin therapy at 84 +± 11 was many standard deviations out of the entire group.

The paradox here is that even with higher fasting insulin levels the fat oxidation rate in the diabetics indicates that the additional fasting insulin levels didn’t seem to stop the diabetics from being able to burn fat. The paradox is that the fat oxidation rate decreased with Insulin Therapy which would indicate the opposite conclusion.

This fits the hypothesis that Insulin Resistance in the liver is a primary driver rather than insulin resistance in adipose cells.

Calories out is much more complicated than just a number on a paper.