Henrik Borg

Islet autoantibodies in the prediction of diabetes in school children

In 1987 serum was collected from 1031 non-diabetic schoolchildren in the Southeast area of Sweden with the aim of evaluating islet autoantibody status (ICA, GADA and IA2-ab) in the prediction of diabetes in schoolchildren. The clinical development of Type 1 diabetes in the children was assessed in 1994 and 1997. The combination of ICA, GADA and IA2-ab were found in four subjects whereas six had two and 35 children one of these antibodies. After 10 years, six of the 1031 children had developed clinical diabetes and five of these six children were positive for islet antibodies. Two were positive for all three antibodies, two were positive for ICA and GADA, and one was positive for GADA. Among the individual autoantibodies, ICA showed the highest positive predictive value (29%) whereas the predictive value for the combination of two autoantibodies was highest for GADA and ICA (40%). Thus, GADA and ICA measurements may be a rational approach to detect schoolchildren at risk for developing diabetes.

Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune type 1 diabetes in children older than 3 yr of age.

Abstract: Background:  Insulin autoantibodies (IAA), antibodies against endogenous insulin, may be detected in type 1 diabetic children before the start of insulin treatment.

Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes

ObjectiveTo investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non‐autoimmune (type 2) diabetes in young adults. Material and methods Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15–34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody‐negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3–4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Results Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2–3‐fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01–0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut‐off, the sensitivity and specificity for differentiation between autoimmune and non‐autoimmune diabetes were 87% and 92%, respectively. At 3–4 months after clinical onset of diabetes, proinsulin secretion was still 2–3 times higher in type 2 than in type 1 diabetes patients (p<0.001). Conclusions. Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non‐autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.

Islet antibodies associated with pancreatic B‐cell dysfunction at and 3 years after diagnosis of diabetes in subjects aged 35–64 years old: degree of impairment less severe than in those aged 0–34 years old

Aims  To determine differences in pancreatic B‐cell function in relation to islet antibodies at diagnosis of diabetes and 3 years later in subjects aged 35–64 years old compared with those aged 0–34 years.

Perioperative serum cortisol levels in ACTH sufficient and ACTH deficient patients during transsphenoidal surgery of pituitary adenoma

PurposeNo previous study has analyzed serum cortisol levels during transsphenoidal endoscopic pituitary surgery in patients with and without hydrocortisone (HC) substitution.MethodsA total of 15 patients undergoing surgery for a pituitary adenoma were studied. Those with normal ACTH function were either not given HC (n = 7) or received 50 mg intravenous HC at the start of surgery (n = 4). Patients with ACTH deficiency received intravenous HC of 100 mg in the morning before surgery (n = 4) with the additional 50 mg for an afternoon operation (n = 2). Propofol and remifentanil were used as anesthetics. Serum cortisol was measured at the start of and every 30 min during surgery.ResultsAmong 7 patients with normal ACTH function without HC substitution, cortisol levels before surgery were 126–244 nmol/L, among the 4 patients undergoing surgery in the morning, whereas the 3 who underwent surgery in the afternoon had lower levels, 38–76 nmol/L. During nose/sinus surgery cortisol levels decreased to 79–139 and 24–54 nmol/L, respectively. At intrasellar manipulation a distinct rise was noted. Also, in the 4 ACTH sufficient patients receiving HC, cortisol levels decreased during nose/sinus surgery, but only with a slight increase during intrasellar surgery. In the 4 ACTH deficient patients cortisol peaked at 1914–2582 nmol/L.ConclusionsPatients with normal ACTH function without HC substitution had very low cortisol levels during the first part of surgery, likely suppressed by the anesthetics. After mechanical impact in the sella, a marked increase in cortisol was noted. Supraphysiological cortisol levels were achieved with our routine HC substitution, advising us to reduce the supplementation.