“Insulin is a double-edged sword with a pointy tip” discussed the relationship between insulin and visceral fat. In brief, any dietary intervention which lowered insulin concomitantly reduced visceral fat, and this was accompanied by a variety of health improvements. Today’s post focuses more on the connection between insulin and body composition. Current hypothesis: reducing insulin causes weight loss, and this weight is primarily adipose (muscle is spared). IOW, insulin plays a primary [cause], as opposed to secondary [effect] role in regulating fat mass. FYI the alternative hypothesis states that reduced insulin levels are simply one of the many beneficial effects of weight loss.
Exhibit A: lower insulin is correlated with more fat loss
1. Diet-induced reduction in insulin
Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial (Das et al., AJCN 2007)
In this year-long study, the low glycemic load (GL) diet reduced insulin levels to a greater degree than the high GL diet (-21.2% vs. -18%), and this resulted in more total fat loss (-26.1% vs. -23.5%), and a greater proportion of the total amount of weight lost was comprised of fat (92% vs. 81%). The differences were small, but probably not due to chance given the consistency and specificity of this effect (see below).
B. Calories vs. carbs
The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets (Brehm et al., 2005 JCEM)
In this 4 month-long study, the low-carb diet lowered insulin over twice as much as the low-fat diet (-36.8% vs. -13.6%), which resulted in significantly more total fat loss (-6.7% vs. -3.8%), and a greater proportion of the total weight lost was comprised of fat (92% vs. 81%). The absolute differences between studies (comparing these results directly to the above results) are big, but this is not unexpected because each study has markedly different 1) patient populations, 2) study durations, and 3) interventions.
2. Exercise-induced reduction in insulin
Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men (Ross et al., 2000 Annals of Internal Medicine)
In this rather complicated 3 month-long study, the exercise group lost weight, and this was compared to a group who lost a similar amount of weight by diet alone. The diet-alone group functioned as a control for the negative energy balance. Exercise lowered insulin levels more than diet alone (-41.4% vs. -17.9%), which resulted in more fat loss (-18.4% vs. -16.9%), and a greater proportion of the total weight lost was comprised of fat compared to diet alone (81.3% vs. 64.9%). If a greater proportion of the total weight lost was comprised of fat, then the intervention selectively spared lean mass resulting in a more favorable body composition; this occurs consistently in every study mentioned in this post.
Exhibit B: pharmacologically lowering insulin causes fat loss
1. Diazoxide
Beneficial effect of diazoxide in obese hyperinsulinemic adults (Alemzadeh et al., 1998 JCEM)
Diazoxide directly targets the pancreatic beta-cells to reduce glucose-stimulated insulin secretion. In this 2 month-long study, diazoxide combined with a low-calorie diet reduced insulin levels more than diet alone (-35.7% vs. -14.7%), which resulted in more fat loss (-19.8% vs. -6.8%), and a significantly greater amount of the total weight lost was comprised of fat compared to diet alone (95% vs. 72%).
2. Octreotide
Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome (Gambineri et al., 2005 JCEM)
Octreotide is a somatostatin analogue which suppresses, among other things, insulin secretion. In this 7 month-long study, octreotide combined with a low calorie diet reduced insulin levels more than diet alone, which resulted in more fat loss (-6.4% vs. -2.4%), and a greater proportion of the total weight lost was comprised of fat.
Exhibit C: insulin increases fat mass
The previous data supported the hypothesis that lowering insulin, by multiple completely different mechanisms, results in reduced fat mass. The next evidence argues against the opposite hypothesis and supports a direct role for insulin in increasing fat mass.
Causes of weight gain during insulin therapy with and without metformin in patients with type II diabetes mellitus (Makimattila et al., 1999 Diabetologia)
In this year-long study, diabetic hyperglycemia was treated with insulin alone or insulin combined with metformin. All subjects in this study gained weight and fat mass. The addition of metformin to insulin therapy blunted the increase in insulin levels (30.8% vs. 45.5%), which reduced fat gain (11.6% vs. 22.1%), and only 73.7% of the weight gained was fat compared to 91.8% by insulin alone.
Administration of exogenous insulin increases fat mass. Reducing insulin, by a variety of means, burns fat and spares lean mass.
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