The Flatline Days

Almost done with insulin infusions, thankfully. This post follows on from the initial post here.

It's time to discuss the discussion and then leave this paper for ever. Here's your starter for 10, and I quote:

"These three studies suggest the following: (1) insulin limits meal size when blood levels are modestly elevated for prolonged periods of time in the rat, (2) this decrease in meal size is not compensated for by an increase in meal frequency and, hence, total daily food ingestion and body weight gain are reduced, and (3) this effect appears to be a heightening of satiety rather than an induction of illness."

and at the end of the discussion:

"...it seems probable that our prolonged, modest elevations of insulin resemble the elevated basal plasma insulin induced by prolonged overfeeding and perhaps, obesity."

Let's combine suggestions (1) and (2) and drop down to our local McMuffin restaurant to watch the people eat. I've never tried this, so you have to realise I'm making all of this up, in its entirety.

In comes Jo Blob at 400kg, fasting plasma insulin at 100microIU/ml. Obviously this fasting hyperinsulinaemia blunts his appetite and he turns down the "you wanna supersize that?" offer, sits picking at his fries and soda for half an hour and eventually pushes the burger-in-a-bun away after three mouthfuls as his satiety hormone has kicked in, to even higher levels than it was when he was fasting.

Across the aisle sits Dr Guyvernment at 55kg with a fasting insulin of 5microIU/ml. Where is his satiety? Obviously he is ravenous and after the double baked potato with a baked potato on the side and three baked potatoes to follow, he's still ravenous because he is so insulin sensitive that he can't get his satiety hormone level over diddly squat.

It's the age old story. Skinny people overeat because their insulin levels are low and and fat people are chronically over sated so refuse food. Have you noticed anything along these lines? No? Somewhere along the line we do have to have a reality check!

The next statement from the discussion which caught my attention was this one:

"As pointed out earlier, some animals which received the higher dosage of insulin showed hyperphagia, as has been reported in numerous other studies [3. 8, 9, 11, 15]. It is probable that animals which became hyperphagic were more insulin sensitive and perhaps increased food intake to counteract hypoglycemia."

Okaaaay. This suggests that the animals on 6iu/24h over-ate. On average. I hate to query the obvious but does this imply the animals on 1iu/24h didn't overeat? So of course this means that the 6iu/24h animals must have gained more weight due to their hyperphagia. So did the 6iu/24h group really gain extra weight compared to the 1iu/24h group? Go look at Fig 1. Here it is again if you've forgotten:



Duuuuh. The 1iu/24h group gained more weight than the (partially hyperphagic) 6iu/24h group, even if p never got below 0.05. The people who wrote the quoted text are the same people who drew the graph... They have the daily food intakes and weight gains for each individual rat...



And finally, before I leave this execrable paper for ever, are the animals on insulin pumps just ill from their insulin infusion? Let's quote the authors again:

"We realize that a simpler explanation for our results might be that the animals become sick following the release of the insulin, however, we offer two arguments against this. First, water intakes were not decreased by insulin infusions from the Minipumps but were elevated by an average of 47.3% during the first 2 days following pump implantation and then returned to normal. Following this initial elevation, water intakes were not significantly different from controls (0 U/day animals) and the pump-implanted animals’ own baselines..."

Never mind the second argument. Let's think about polydipsia (and presumably polyuria because weight didn't increase) as markers of robust good health in a patient, any patient. I'll use a make-believe, utter fantasy, clinical setting:


Dr Insulin: Ah, hello Mrs Ratty, how are you since I implanted your insulin infusor pump two days ago, to help control your appetite?

Mrs R: I can't seem to stop drinking. I've always got to have a bottle of Evian by my side and I'm spending 47.3% more on the stuff. I wake up in the night to have a drink and I always seem to be spending a penny.

Dr I: Excellent, a good thirst is always my first maker of robust health.

Mrs R: Oh, so you won't need this urine sample I've brought?

Dr I: Oh no, no need to check your urine if you have a healthy thirst.

Mrs R: So I can throw it away?

Dr I: Of course. By the way, is that your sample in the five litre container? Could I oblige you by assisting with its disposal?

Mrs R: Thank you so much, it is quite heavy. You are so helpful. Goodbye.

Dr I: Goodbye (and after Mrs R has left): Igor, IGOR! Come, never mind the LIRKO mice, we have jam a-plenty tonight. Boil down this sample at once...



Okay. If a rat on a pump giving a constant rate infusion of insulin gets Somogyi overswing, how long does it take for the overswing to correct itself, while ever insulin levels are held constant?

I would guess two, at the most three, days. The Flatline Days. When glucose is high and appetite is consequently low. Pure speculation. It would have taken 30 seconds on a urine glucose test stick to check this. They had the sticks.

Peter