Thus there is a general consensus that diabetes is associated with progressive and cumulative processes that are much more amenable to retardation than to reversal. Nevertheless, from a clinical perspective, reversing pathologies associated with diabetes would be far more valuable than simply delaying their onset…
…We have proposed that both diabetic complications and age-related pathologies develop due to a progressive and cumulative effect of glucose metabolism that produces a bistable hysteretic effect on gene expression…
…In addition to glycolytic enzymes that would be expected to produce oxidative stress, glucose metabolism also induces a variety of molecular responses such as thioredoxin-interaction protein and p65 that could plausibly contribute to nephropathy. Indeed, the latter induction is persistent, even after normalization of glucose, thus exemplifying glucose-induced hysteresis and its clinical correlate, metabolic memory, including in nephropathy…
…Furthermore, based particularly on detailed analysis of the hysteretic behavior of the lac operon, we have hypothesized that sufficiently prolonged and robust reduction in glucose metabolism or molecular responses to glucose metabolism may reverse this bistable molecular state, leading to reversal of pathology…
…Together with evidence suggesting that the ketogenic diet produces a prolonged exposure to 3-OHB, these data suggest that the ketogenic diet may prevent and even reverse pathologies associated with diabetes…
…In the present studies we therefore examined if a ketogenic diet would reverse pathologies produced by diabetes. We focused on nephropathy because kidney function is relatively amenable to repetitive assessment simply by repetitive collection of urine, thus allowing definitive determination that pathology had developed before beginning the dietary intervention. These studies clearly demonstrate that diet can reverse diabetic kidney disease even after it has developed.