I think there’s some useful insight into one Oral Diabetes medication in the following originally from Aug 8, 2016.
The phrase “stimulates glucose uptake by cells” is equivalent to “helps lower insulin resistance”. From this paper (Hundal RS, Krssak M, Dufour S, et al. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000;49(12):2063-9), you can see why Metformin works and how it doesn’t quite work well enough in a diabetic person.
The rate of glucose production was twice as high in the diabetic subjects as in control subjects (0.70 ± 0.05 vs. 0.36 ± 0.03 mmol · m−2 · min−1, P < 0.0001). Metformin reduced that rate by 24% (to 0.53 ± 0.03 mmol · m−2 · min−1, P = 0.0009) and fasting plasma glucose concentration by 30% (to 10.8 ± 0.9 mmol/l, P = 0.0002).
So diabetics produced 2x the insulin of non-diabetics (100%) but Metformin only reduced that rate by 24%. Better than nothing but not nearly enough to make the diabetic person “normal”. And insulin resistance is a progressive disease by which the cells get better and better at not unlocking for insulin.
Going on in the paper.
The rate of gluconeogenesis was three times higher in the diabetic subjects than in the control subjects (0.59 ± 0.03 vs. 0.18 ± 0.03 mmol · m−2 · min−1) and metformin reduced that rate by 36% (to 0.38 ± 0.03 mmol · m−2 · min−1, P = 0.01). By the 2H2O method, there was a twofold increase in rates of gluconeogenesis in diabetic subjects (0.42 ± 0.04 mmol · m−2 · min−1), which decreased by 33% after metformin treatment (0.28 ± 0.03 mmol · m−2 · min−1, P = 0.0002).
It keeps getting better. A diabetic person is 3x better at gluconeogenesis but Metformin was only able to reduce that so that the diabetic person was at 2x the normal person.
And note, Metformin is about as good as it gets in that category of drug. Looks like it can help, but not solve the issues with gluconeogenesis. Something is better than nothing but don’t get lulled (like I was) into assuming all is well. If we keep filling up those protein stores than the same problem which happened to us with carbs will also happen to us with proteins.
Fatty Liver and Metformin
A randomized, double-blind, placebo-controlled trial to test whether metformin improves liver histology in patients with non-alcoholic fatty liver disease (Scand J Gastroenterol. 2009;44(7):853-60. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Haukeland JW1, Konopski Z, Eggesbø HB, von Volkmann HL, Raschpichler G, Bjøro K, Haaland T, Løberg EM, Birkeland K.).
Forty-eight patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) were randomized to treatment with metformin (n=24) or placebo (n=24) for 6 months.
The study concluded that:
Treatment with metformin for 6 months was no better than placebo in terms of improvement in liver histology in patients with NAFLD.
Could it be because the liver is already full and can’t get fatter?
I still thought it was protein in the diet that was the problem with GNG. There’s some dispute in the literature about whether GNG is affected by the fat in the liver or not (Nutrients. 2013 May; 5(5): 1544–1560. Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease Melania Gaggini, Mariangela Morelli, Emma Buzzigoli, Ralph A. DeFronzo, Elisabetta Bugianesi, and Amalia Gastaldelli).
It looks like the final word may be in this study (Gastroenterology. 2007 Aug;133(2):496-506. Epub 2007 May 1. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastaldelli A1, Cusi K, Pettiti M, Hardies J, Miyazaki Y, Berria R, Buzzigoli E, Sironi AM, Cersosimo E, Ferrannini E, Defronzo RA.). The study found that fat in the liver wasn’t the source of GNG, but visceral fat tissue.
Excess VAT primarily increases GNG flux.
Protein doesn’t turn to chocolate cake. Your Dawn Syndrome isn’t from the chicken you had last night. It’s from the cookies you ate three years ago.