Residual insulin production, glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term Type 1 (insulin-dependent) diabetes mellitus

Abstract

The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9-16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (greater than or equal to 0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9 +/- 0.3% vs 7.9 +/- 0.3%, (p less than 0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the non-excretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) greater than or equal to 5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l:mmol/l X 10) greater than or equal to 136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p = 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Diazoxide Treatment at Onset Preserves Residual Insulin Secretion in Adults with Autoimmune Diabetes

“…The C-peptide level differed significantly from that of the placebo-treated control group at 12 and 18 months. This finding is of interest since it has been previously shown that the presence of minute residual (3-cell function in patients with longterm IDDM confers better glycemic control (11)(12)(13), which in itself according to the evidence presented from the Diabetes Control and Complications Trial is associated with a remarkable reduction in the risk of long-term complications (14). In the present study of 20 patients, no difference in metabolic control between the two treatment groups was observed.…”

C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells

“…As a consequence, individuals with type 1 diabetes have severely reduced levels or absence of C-peptide; this is considered an important factor in the pathophysiology of diabetic complications. In fact, people with type 1 diabetes who retain a low but detectable level of C-peptide are less prone to develop microvascular complications of the eyes, kidneys and peripheral nerves [24][25][26]. Moreover, pancreas or islet transplantation, with restoration of endogenous insulin and C-peptide secretion, is known to be accompanied by improvement of diabetes-induced abnormalities of nerve function, endothelial function and both structural and functional changes of the kidneys [37,38].…”

“…C-peptide, the cleavage product of the proinsulin molecule in the pancreatic beta cells, has been shown to exert insulin-independent biological effects on a number of cells, proving itself as a bioactive peptide with antiinflammatory properties [23]. As type 1 diabetes patients typically lack physiological levels of insulin and C-peptide, this is considered an important factor in the pathophysiology of diabetic complications [24][25][26]. C-peptide has been shown to improve endothelial dysfunction and systemic inflammation in several in vivo and in vitro models of inflammation-mediated vascular injury by reducing expression of genes encoding endothelial cell adhesion molecules, inflammatory cytokine production and adherence and transmigration of leucocytes [27][28][29][30].…”

Does C-peptide have a physiological role?

“…Residual insulin secretory activity in these patients has been suggested to be associated with improved blood glucose control in cornparison with patients without such activity [15,16]. Likewise, early signs of microvascular lesions are observed more frequently in patients without signs of residual beta-cell activity [14]. In addition, a negative relationship has been demonstrated between endogenous beta-cell activity and early signs of diabetic retinopathy, as evaluated by vitreous fluorophotometry; this correlation was more marked than that between glycaemic control and early retinopathy [17].…”

“…Some patients with IDDM maintain a level of pancreatic beta-cell activity for many years after onset of the disease [13,14]. Residual insulin secretory activity in these patients has been suggested to be associated with improved blood glucose control in cornparison with patients without such activity [15,16].…”