Natural Course of Insulin Resistance in Type I Diabetes

Abstract

To examine the natural course of insulin action in Type I diabetes, we followed 15 patients prospectively for one year after the diagnosis of diabetes and also performed a cross-sectional study of 53 additional patients who had had diabetes for 2 to 32 years. Two weeks after diagnosis, the rate of glucose uptake during hyperinsulinemia, a measure of insulin action, was 32 percent lower in the patients with diabetes than in 30 matched normal subjects (P less than 0.01), but it rose to normal during the subsequent three months. At three months after diagnosis, 9 of 21 patients (43 percent) were in clinical remission and did not require insulin therapy. In these patients, insulin action was 40 percent greater (P less than 0.002) than in the patients who continued to need insulin treatment. Fasting plasma C-peptide levels were slightly but not significantly higher in the patients who had a remission than in the other patients. In patients who had had diabetes for one year or more, insulin action was also reduced by an average of 40 percent (although there was considerable variation between patients), and it was inversely related to glycemic control and relative body weight. Thus, in patients with newly diagnosed Type I diabetes, a transient normalization of insulin action may occur after an initial reduction, along with a partial recovery of endogenous insulin secretion, and these events may contribute to the development of a clinical remission ("honeymoon" period). A majority of patients with diabetes of long duration are characterized by varying degrees of insulin resistance.

Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

“…This finding supports the suggestion of a protective role of CCL4 to β-cell during diabetes progression [23,24]. The missing association of CCL4 with remission that was defined by metabolic control and insulin requirement might be explained by the reason that remission is caused by different factors than just β-cell function [31,32].…”

Role of insulin resistance in the pathogenesis of NIDDM

“…In any type of diabetes, NIDDM [103], IDDM [104,105] or pancreatogenic [106], insulin sensitivity is impaired compared to matched non-diabetic individuals. In patients with IDDM, insulin sensitivity is normal if glycaemic control is normal, as in patients who are in clinical remission [107], or in whom glycaemic control has been normalized by intensive insulin therapy [108][109][110].…”

“…In patients with NIDDM, any intervention which lowers plasma glucose concentrations seems to improve insulin sensitivity [111]. The degree of insulin resistance is inversely correlated with average glycaemic control in both patients with NIDDM [2,112,113] and IDDM [105,114]. Direct proof of the ability of hyperglycaemia per se to induce insulin resistance has been obtained in studies in patients with IDDM [115,116] as well as in studies performed in diabetic …”

“…The glucose infusion rate required to maintain normoglycaemia between 20-120 min was used as the measure of whole body insulin sensitivity. Unpublished data and data from references [25,31,105,[121][122][123] Variation in insulin action in normal subject~"…”

Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in G�ttingen minipigs

“…Combined with dietaryinduced insulin resistance, the present model could display insulin resistance combined with blunted insulin secretion, thus carrying the two major characteristics of Type 2 diabetes, but in our study, defects more likely reflect LADA. To further support that primary beta-cell loss fails to result in Type 2 diabetes, data in other animals show normal insulin sensitivity after NIA+STZ, as is seen in honeymoon diabetic patients [31,32]. The present model, however, might be very suitable for studies on pharmacological intervention to improve residual beta-cell mass.…”