Does Insulin Status Predict Carbohydrate Tolerance?

Does Insulin status predict ‘Carb Tolerance’?

By: Cliff Harvey, PhD candidate in nutrition (AUT)

Read Time: 0.67 bowls of pappardelle pasta with fresh grated Parmesan.
Reviewed and Edited by: Brad Dieter, PhD

There is a running debate in nutrition between advocates of lower-carbohydrate nutrition and higher-carbohydrate nutrition. Low carbohydrate devotees often tout purported (and often incorrect or incomplete) assumptions such as: the ‘insulin hypothesis’ of fat gain as well as the supposed ‘metabolic advantage’ of low carb diets. On the other hand, devotees of higher carb nutrition point to in vivo evidence of the efficacy of higher carb nutrition strategies for a range of outcomes and the inconsistencies within the oversimplified theories of insulin and fat gain, and metabolic advantages of low carb.

While the insulin hypothesis of fat gain is at best incomplete, and at worst highly erroneous*, insulin, as one of the hormones (along with glucagon) primarily involved with glucose homeostasis, its relative production, release, and uptake, are likely to be involved with the ‘tolerance’ to greater carbohydrate loads.

There is some evidence  that people with relative hyperinsulinaemia and insulin resistance (IR) respond more favourably to a low-carbohydrate diet, while those people more insulin sensitive (IS) get better results from a higher carbohydrate diet. Insulin Resistance is the state in which cells begin to fail to respond to insulin. This typically results in hyperinsulinaemia (high insulin levels) and eventually, can lead to diabetes. However, in the early stages of pre-diabetes and IR, blood glucose levels may remain within a normal range. Many of the proxy markers for IR used in research (such as fasted insulin, HbA1c, triglycerides, and even oral glucose tolerance challenges) are not always indicative of insulin signalling or resistance. Clinically, we would typically look at a range of markers, especially triglycerides and other lipids, HbA1c, liver enzymes,  and abdominal girth as indicators of insulin resistance but even these in combination are not wholly accurate.

To date, there are four randomised controlled studies that have looked at how low-carb or low-fat diets impact metabolism and weight loss in insulin sensitive and insulin resistant people.

Pittas and colleagues demonstrated that those with above-median insulin response (30 min after glucose load) lost more weight over a 6-month period when consuming a low–glycaemic load diet compared with a high glycaemic load diet (10 kg vs 6 kg)(p < 0.05).1 The reverse was observed in the lower-insulin group, who lost more weight following a high–glycaemic load diet (8 kg vs 6 kg), but the difference was not statistically significant (p = 0.25). In this study however, protein intake differed between the groups with the lower-carb group allocated 30% of calories, versus the higher-carb group allocated 20%.

Similar results were demonstrated in a study comparing obese non-diabetic insulin-sensitive (fasting insulin < 10 microU/mL; n = 12) with obese non-diabetic insulin-resistant (fasting insulin > 15 microU/mL; n = 9) women, randomised to receive either a high carbohydrate, low fat (HCLF) (60% CHO, 20% fat) or lower carbohydrate, higher fat (LCHF) (40% CHO, 40% fat) hypocaloric diet. Insulin-sensitive women lost 13.5 +/- 1.2% (p < 0.001) of their initial BW on a high-carb diet, whereas those on the LCHF diet lost 6.8 +/- 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, insulin-resistant women on the LCHF diet lost 13.4 +/- 1.3% (p < 0.001) of their initial BW as compared with 8.5 +/- 1.4% (p < 0.001) for those on the HCLF diet (p < 0.04 between two groups).(Figure 1.)

Figure 1. Absolute (A) and percentage (B) change in BW in IS and IR women randomized to 16 weeks of hypocaloric HC/LF or LC/HF diet. (*) p < 0.01 for diet effect within IS group. (†) p < 0.05 for Si effect within HC/LF diet. (‡) p < 0.05 for diet effect within IR group. (§) p < 0.01 for Si effect within LC/HF diet.

Likewise, in a 6-month, randomised controlled trial of 73 obese young-adults, serum insulin concentration at 30 minutes after a 75 g dose of oral glucose was determined at baseline as a measure of insulin secretion. A lower-carbohydrate diet (40% carbohydrate and 35% fat) was compared to a low-fat (55% carbohydrate and 20% fat) diet. While there was little difference between the two groups overall, those in the lower carbohydrate group that displayed values above the median insulin concentration at 30 min post glucose load (i.e. the ‘more’ insulin resistant participants) had a greater reduction in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03) than those in the low-fat group at 18 months. Cardiometabolic markers were not significantly different in relation to this modifier.3 Similarly in a study of 245 overweight and obese women, while there was no significant difference in weight loss between lower and higher carbohydrate diet groups overall, insulin sensitive participants achieved greater weight loss on a higher carbohydrate diet. Average weight loss was 7.5% of initial weight in the total sample, and insulin‐sensitive women assigned to the lower fat diet lost more weight than those assigned to the lower carbohydrate diet (8.3% [SEM 1.0%] versus 5.4% [1.0%], respectively; p <0.05). No difference was observed in those IR following a lower- or higher-carb diet, averaging 7.2% (SEM 1.0%) and 8.7% (SEM 0.9%), respectively.4

 A pilot trial to investigate these effects in an ad-libitum diet over six-months found increased weight loss resulting from low-carbohydrate diets in insulin-resistant participants over insulin sensitive and improved weight loss resulting from low-fat diets for insulin sensitive participants, (weight loss of 7.4 ± 6.0 (LF-IR), 10.4 ± 7.8 (LF-IS), 9.6 ± 6.6 (LC-IR), and 8.6 ± 5.6 (LC-IS)). (Figure 2.) Also noted were (non-significant) improvements in HDL, triglycerides, fasting glucose and insulin, and blood pressure for low-carb diets versus high-carb in those more insulin resistant. In those more insulin sensitive, the low carbohydrate diet improved HDL and triglycerides more than that of the low-fat diet, whereas the low-fat diet resulted in improved fasted insulin and glucose.5

Figure 2. Six-month weight change by diet and insulin resistance group, n = 49. Six-month weight loss (kg) was 7.4 ± 6.0 (LF-IR), 10.4 ± 7.8 (LF-IS), 9.6 ± 6.6 (LC-IR), and 8.6 ± 5.6 (LC-IS).

While not specifically addressing insulin resistance vs sensitivity, an RCT conducted by Tay and colleagues suggested improved outcomes for triglycerides (VLCHF -0.64 +/- 0.62 mmol/l, HCLF -0.35 +/- 0.49 mmol/l; p = 0.01) and increases in HDL cholesterol (VLCHF 0.25 +/- 0.28 mmol/l, HCLF 0.08 +/- 0.17 mmol/l; p = 0.002), from a very low carb diet vs high carb diet, with no change in LDL and no difference between weight lost, in a cohort of abdominally obese participants (likely to be IR).6

 It’s also been demonstrated that IR participants were less likely to adhere and therefore to lose weight on a low-fat diet, compared to insulin-sensitive (IS) participants. However, in one  study, adherence and weight-loss were similar between both IR and IS participants allocated to a low-carb diet.7

 These studies suggest a few things.

  • Regardless of diet composition, weight loss improves cardiovascular and metabolic markers.
  • Lower carb strategies are likely to provide more benefit  than higher carb for those who are insulin resistant, at least in the short- to medium-term. These benefits range from miniscule to moderate, and likely depend on the population.  More studies need to pin down the magnitude of these effects.
  • Even relatively small reductions in carbohydrate intake improve outcomes for those who are insulin resistant.
  • Those who are more insulin sensitive are likely to benefit from higher carbohydrate diets.
  • Insulin-sensitive people adhere equally well to low-carb or low-fat diets, but insulin resistant people adhere better to low-carb diets.**

It is important to note that kind of like an Oprah Show, where everyone gets a prize, in the studies above, everyone lost weight!

While results were improved for those more insulin sensitive from the higher carbohydrate diets, and for those insulin resistant on the lower carb diets, everyone lost weight due to the calorie restricted nature of the diets overall. The Gardner study was the exception as it used a ‘limbo-titrate-quality’ model in which participants restricted fat or carbohydrate to as low as possible (around 5 g), then titrated either fat or carbohydrate dose by 5 g to personal tolerance and ability to adhere over several months. It was ad libitum, and focused on quality of eating, using subjective terms like “real food,” “minimally processed,” “seasonal,” “organic,” “grass-fed,” “whole grain,” and “pasture-raised,” depending on diet assignment. As with the other studies, it contained a relatively minor carbohydrate restriction, and, due to a paucity of evidence, it’s unclear whether a greater carbohydrate restriction would provide greater benefits for those people more insulin resistant. Unlike the Pittas study, in which protein intake differed between the LC and HC groups, in the studies by Cornier et al. and Ebbeling et al. protein was matched (20% and 25% respectively) while in the Gardner et al. study ad libitum protein intake between the groups differed little; 25% of calories in the lower-carb group and 22% in the higher. Thus, in these instances protein intake was unlikely to be a determinant of any differences in results.

Systematic reviews show that when calories are restricted, there is little difference in outcomes including weight, total or LDL cholesterol, and diastolic blood pressure for those with Type 2 diabetes (who will by proxy be IR).8-12 Notwithstanding this, the greater the carbohydrate restriction, the greater the glucose-lowering effect,11 and low-carb diets result in greater improvements in HDL, HbA1c, and systolic blood pressure among Type 2 diabetics.12*** It’s also been noted that adherence is more difficult with extreme carbohydrate restriction (i.e. <50 g of carbohydrate per day),12 but that a more moderate restriction is effective and as noted, those IR adhere better to a low-carb diet than a high-carb diet.

Could there be a metabolic advantage if calories were habitual, not restricted?

It’s interesting to consider what might happen if these short- or long-term studies were eucaloric (i.e. using habitual calories). Would there be a differential effect, such that at a baseline of calories there would, in fact, be a ‘metabolic advantage’ (resulting in for example increased body fat loss) from either a lower or higher carb diet depending on your insulin status? That is a question that currently remains unanswered, but we hope to add to the knowledge in that area with upcoming publications on eucaloric diets differing in carbohydrate content.****

Other considerations and caveats

Lack of clear definitions of ‘low carbohydrate’ diets

I hate to be ‘that guy’ who claims any low-carb study that doesn’t show significant outcomes is due to the diets not being ‘low enough’ in carbohydrate…BUT most of these studies wouldn’t typically be considered ‘low carb’ by anyone except for nutrition nerds (I mean researchers), for whom low-carb can mean anything up to 40-45% of calories,13, 14 but they do show a trend towards improved results for those with IR resulting from even minor carbohydrate restrictions. It will be interesting to see if greater results are improved with greater carbohydrate restriction in those with greater IR (a hypothesis we are currently testing in our research at AUT University).

 Proxy measures of IR

The results from the studies on ‘IF v IS’ must be interpreted cautiously as the measures of insulin sensitivity used are inexact. Fasted glucose and insulin and insulin in response to a standard glucose tolerance test are all considered inexact. Better testing methods might be full ‘Kraft assays’ measuring both glucose and insulin at 30 min intervals following an oral glucose challenge of 75 grams of glucose in conjunction with C-peptide, and markers associated with IR such as HbA1c and serum triglycerides. We must also consider that studies in those with type 2 diabetes may not accurately reflect those with insulin resistance as, although those with Type 2 diabetes will be insulin resistant, many people with pre-diabetic insulin resistance can express normal fasted glucose and HbA1c measures.

 Change in insulin status over time

If the hypothesis that insulin resistance improves over time with a lower carbohydrate diet is correct, especially when combined with appropriate overall calories and resistance training, then it stands to reason that carbohydrate tolerance would also improve over time and therefore carbohydrate intake could increase somewhat over time too.

Ad libitum vs calorie controlled diets

Many of the (especially earlier studies) included in reviews and meta-analyses compare calorie restricted high carbohydrate diets to ad libitum lower carbohydrate diets (such as those by Brehm et al.,15 Ebbeling et al.,16 and others). As adherence and compliance are keys to dietary success, any diet that allows you to auto-regulate your calorie intake, whether higher or lower carb, is likely to be superior to a diet that requires more aggressive control in order to be successful.

Carbohydrate intake is ‘activity dependent’

Exercise will necessitate increased relative fuel intake, including carbohydrate, especially for activities involving repeated bouts of intense effort at >10 s up to several minutes. So, even if you are a low-carb responder, your low-carb diet should contain more relative carbohydrate with greater levels of activity, even if remaining low carb. On a side note, this is why I prescribe carbohydrate and fat, appropriate to the individual as a % of total calories, not as absolute gram amounts.

Interpretation

The take-home message is that people with insulin resistance may be slightly better on a lower carbohydrate diet, all else held equal.   Conversely, insulin sensitive  people may benefit from greater amounts of carbohydrate in the diet in the short to medium term.

Overall though, even if a lower or higher carb diet was supposedly the ‘best’ diet for you, and might provide, in the short-term, some improvements (based on your insulin status), it may not be the best fit for your lifestyle or tastes. When it comes down to it, behavioural factors and adherence to a diet over a longer term are the most important factors for success. So, if you restrict calories by any means, you’re likely to reduce weight, fat, and cardiometabolic risk factors and at the end of the day, you’re going to get the best results from any nutrient-dense, calorie-appropriate diet that you can stick to.

Editor’s Notes
Cliff initially brought this idea to me during a discussion on our Facebook Page and I wanted to explore the idea of the idea of stratifying diet based on insulin sensitivity. The data presented in the present article provide a foundation to suggest that there may be a benefit for modifying macronutrient ratios based on insulin sensitivity. While very intriguing and promising data it is important to understand the context of these data as Cliff articulates in the Interpretation section; specifically, that the adherence, longevity of the dietary intervention, and weight loss.  After these factors are accounted for, then the stratification would likely be of some small benefit.

*Data over the last decade has clearly shown that in humans, dietary carbohydrate and the insulin response it releases is not a major player in fat gain or fat loss in the overall context; the carbohydrate-insulin hypothesis as traditionally thought of has a large amount of data to refute it and very little to support the. The current question of optimizing weight loss is a substantially different question.

** The data from the paper that indicates that people who are insulin resistant adhered better to low carbs diets is shown below. My interpretation of this data are that insulin resistant people were less adherent to a low fat diet than Insulin Sensitive people, and similarly adherent to a low carbohydrate diet (as defined in that study).

McClain et al. Diabetes, Obesity and Metabolism 2013

 

***The size of these effects are important to understand. In the meta-analysis published by Huntriss, Campbell, and Bedwell, the low carbohydrate diet produced a 0.28% lower HbA1c, 1.08 mg/dL higher HDL, 4.32 mg/dL lower triglycerides, and a 2.74 mm Hg systolic blood pressure. Also of note: 15 out of the 18 studies in this meta analysis were considered high risk of bias.

**** The hypocaloric studies have been done to a great extent. Eucaloric studies will be important; however, the exercise component of those studies will also be key as we have discussed previously the signals into the body often direct what substrates are used for and would be a big driver of adaptation in eucaloric states.

References

  1. Pittas AG, Das SK, Hajduk CL, Golden J, Saltzman E, Stark PC, et al. A low-glycemic load diet facilitates greater weight loss in overweight adults with high insulin secretion but not in overweight adults with low insulin secretion in the CALERIE Trial. Diabetes Care. 2005;28(12):2939-41.
  2. Cornier MA, Donahoo WT, Pereira R, Gurevich I, Westergren R, Enerback S, et al. Insulin sensitivity determines the effectiveness of dietary macronutrient composition on weight loss in obese women. Obes Res. 2005;13(4):703-9.
  3. Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, Ludwig DS. Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial. Jama. 2007;297(19):2092-102.
  4. Le T, Flatt SW, Natarajan L, Pakiz B, Quintana EL, Heath DD, et al. Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women. Journal of the American Heart Association. 2016;5(1).
  5. Gardner CD, Offringa LC, Hartle JC, Kapphahn K, Cherin R. Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity. 2016;24(1):79-86.
  6. Tay J, Brinkworth GD, Noakes M, Keogh J, Clifton PM. Metabolic Effects of Weight Loss on a Very-Low-Carbohydrate Diet Compared With an Isocaloric High-Carbohydrate Diet in Abdominally Obese Subjects. Journal of the American College of Cardiology. 2008;51(1):59-67.
  7. McClain AD, Otten JJ, Hekler EB, Gardner CD. Adherence to a low-fat vs. low-carbohydrate diet differs by insulin resistance status. Diabetes, Obesity and Metabolism. 2013;15(1):87-90.
  8. Hernández Alcantara G, Jiménez Cruz A, Bacardí Gascón M. [EFFECT OF LOW CARBOHYDRATE DIETS ON WEIGHT LOSS AND GLYCOSILATED HEMOGLOBIN IN PEOPLE WITH TYPE 2 DIABETES: SYSTEMATIC REVIEW]. Nutr Hosp [Internet]. 2015 2015/11//; 32(5):[1960-6 pp.]. Available from: http://europepmc.org/abstract/MED/26545649
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  2. van Wyk HJ, Davis RE, Davies JS. A critical review of low-carbohydrate diets in people with Type 2 diabetes. Diabetic Medicine. 2016;33(2):148-57.
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