I wrote something on this topic a while ago, which I reproduce below:
C-peptide is a natural hormone involved in insulin synthesis. It has long been known that administration of c-peptide to type 1 diabetics up to the normal levels found in healthy individuals can be beneficial in ameliorating characteristic diabetic complications, yet c-peptide accomplishes this without improving glucose utilization in any significant, long-term way, and also without reducing the amount of insulin the patient has to inject. (1) This suggests that its ameliorative action operates independently of both glucose control and insulin dose. Among other positive effects, c-peptide improves the deformability of red blood cells, allowing them to pass through narrow capillaries more readily, thus improving microcirculation; and it promotes vasodilation; it improves the low nitric oxide production in the diabetic endothelium, making the blood vessels healthier; c-peptide promotes renal function. (2) Since patients who either cannot produce any insulin or are producing lower than normal amounts of insulin also necessarily produce correspondingly less c-peptide, it is possible that at least some or perhaps all of the typical complications of diabetes result from a lack of c-peptide. Since c-peptide could be replaced without changing the insulin dose or long-term glucose utilization, it could also be added to a diabetic treatment program without creating its own hypoglycemia risk.
This evidence that diabetic complications have at least two separate causes, insulin deficiency and c-peptide deficiency, with insulin only controlling the long-term glucose utilization, may explain some of the disconnect observed between diabetic complications and glucose control. For example, while patients who have survived 50 years or more with type 1 diabetes have been reported to have an HbA1c value above 10% in some studies, they often have only very mild complications. (3) Significantly, the Joslin Clinic Report on its Gold Medalist survivors (50 years disease duration and more) notes that 66% of them still have residual c-peptide production, which is undetectable in the majority of type 1 diabetics 5 years post-diagnosis or longer. (4) Since there is independent evidence that inflammation in diabetics correlates with their degree of complications, it could be that the same persisting immunological response to pancreatic beta cells which causes this inflammation also causes patients to have a lower c-peptide production from their correspondingly small number of surviving beta cells, so that what inflammation apparently causes might in fact be caused by a lack of c-peptide. (5)
A recent study has interestingly shown that even a very small amount of residual c-peptide production in a patient can have enormous benefits with respect to the development and progress of complications. Even though, in healthy individuals, the normal c-peptide level is, on average, around 0.5 nmol/L, with fasting levels at 0.42 nmol/L and glucose challenge levels at 0.6 nmol/L, this study has shown that in type 1 diabetics a c-peptide level of even just 0.04 nmol/L, a mere 8.4% of normal levels, can have dramatic benefit. (6) Even improvements to this level from extremely small to merely very small levels showed real clinical benefit to the patients, as long as they were above a lower threshold of 0.08 nmol/L. (7) Benefits included reduced risk of severe hypoglycemia, lower HbA1c values, lower risk of retinopathy, and reduced nephropathy risk. (8)
- J. Wahren, et al, “Role of C-Peptide in Human Physiology,” American Journal of Endocrinology and Metabolism (2000) v. 278, pp. E762, E766.
- Ibid., pp. E762-E765.
- G. Gill, et al, “Insulin Dependent Diabetes of Over 50 Years Duration,” Practical Diabetes International (2005) v. 10, n. 2, p. 60; S. Bain, et al, “Characteristics of Type 1 Diabetes of Over 50 Years Duration,” Diabetes Medicine (2003) v. 20, n. 10, p. 808; J. Sun, et al, “Protection from Retinopathy and Other Complications in Patients with Type 1 Diabetes of Extreme Duration,” Diabetes Care (2011) v. 34, n. 4, p. 968.
- Joslin Clinic Gold Medalists Report (online); J. Lachin, et al, “Impact of C-Peptide Preservation on Metabolic and Clinical Outcomes in the Diabetes Control and Complications Trial,” Diabetes, publication ahead of print, October 2, 2013, p. 5.
- W. Zhang, et al, “Inflammation and Diabetic Retinal Microvascular Complications,” Journal of Cardiovascular Disease Research (2011) v. 2, n. 2, p. 96; D. Luis-Rodriguez, et al, “Pathophysiological Role and Therapeutic Implications of Inflammation in Diabetic Nephropathy,” World Journal of Diabetes (2012) v. 3, n. 1, p. 7.
- J. Lachin, et al (note 4), pp. 3-4.
- Ibid., p. 15.
- Ibid., pp. 14-16.