C-Peptide Lack or High Blood Sugar?

Type 1 patients with more surviving beta cells and thus more natural insulin output can achieve much better glucose control than those with none, since they have a buffer of insulin output which is still perfectly tailored to the body’s requirements. But since the pancreas produces one c-peptide molecule for every insulin molecule it manufactures, patients with better blood sugar control will also have higher c-peptide levels. (M. Sassa, et al, "Glycemic instability in type 1 diabetic patients," DIABETES RESEARCH AND CLINICAL PRACTICE, vol. 81, no. 2, p. 190 (2008))

C-peptide used to be thought to be a useless by-product of insulin production, but recent research shows that it may play a decisive role in preventing diabetic complications. Conversely, it may well be a lack of c-peptide, which closely corresponds to high blood sugar levels, which is the actual mechanism which causes diabetic complications, rather than the high blood sugar per se being the culprit. Since the lack of c-peptide and the high blood sugar run in tandem with each other, it is impossible to distinguish by a study such as the DCCT whether lack of c-peptide or high blood sugar is the cause of complications.(Y. Murase-Mishiba, et al, "Fulminant type 1 diabetes as a model of nature to explore the role of c-peptide," EXPERIMENTAL DIABETES RESEARCH, art. JD 819123 (2008))

Scientists have tried injecting diabetics with c-peptide and have found that it alters the expression of genes inherited along with the genes causing type 1 diabetes and may act to prevent the characteristic forms of diabetic nephropathy, neuropathy, microvascular, and macrovascular disease once thought to be caused by high blood sugar. (C. Hills and N. Brunskill, "Cellular and physiological effects of c-peptide," CLINCIAL SCIENCE (LONDON) vol. 116, no. 7, p. 565 (2009); K. Ekberg, et al, "C-peptide replacement therapy and senosry nerve function in type 1 diabetic neuropathy," DIABETES CARE, vol. 30, no. 1, p. 71 (2007); B. Johansson, et al, "Beneficial effects of c-peptide on incipient nephropathy in patients with type 1 diabetes melllitus," DIABETES MEDICINE, vol. 17, no. 3, p. 181 (2001); F. Panero, et al, "Fasting plasma c-peptide and micro- and macrovascular complications," DIABETES CARE, vol. 32, no. 2, p. 301 (2009))

Although c-peptide is a natural substance found in the body, the FDA is forcing one company trying to bring a therapeutic form of c-peptide to market for diabetics to go through the whole long and expensive process of approval as though it were an artificial drug. This may postpone the availability of c-peptide for treatment of diabetic complications by as much as 12 years and cost about three hundred million dollars. Human c-peptide can be obtained, however, from organic chemical supply houses already, and experiments suggest that a therapeutic dose to prevent complications would amount to about 1.5 mg/day of c-petide injected subcutaneously four times a day. It is very expensive, however, and costs about US $ 200 per mg.