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The triad of diabetic ketoacidosis, acute pancreatitis and hypertriglyceridemia is a rare phenomenon, with mortality rates of up to 80%. A unique characteristic of the described case is the co-occurrence of non-immune haemolytic anaemia (NIHA) with the complex triad. It is suggested that this presentation is secondary to hyperlipidemia which leads to increased fragility of erythrocytes due to destabilization of red cell membranes. Supportive treatment with intravenous insulin and blood transfusions is the cornerstone of treatment., Learning Points: The enigmatic triangle of diabetic ketoacidosis (DKA), hypertriglyceridemia and acute pancreatitis is a rare phenomenon occurring in only 4% of DKA cases.This triad can be complicated by non-immune haemolytic anaemia secondary to hyperlipidemia, which leads to increased fragility of the erythrocyte due to destabilization of red cell membranes.Supportive treatment with intravenous insulin administration and blood transfusions is the cornerstone of treatment., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

After sedation with propofol a young man developed milky-white urine. Urinalysis showed a high concentration of uric acid crystals as being responsible. This phenomenon appears to be dose-dependent and is explained in this report. Since it is harmless and self-limiting no extensive analysis is needed when observed.

A young male patient with rapidly progressive and life-threatening pulmonary haemorrhage due to anti-glomerular basement membrane (anti-GBM) antibody disease without renal involvement repeatedly tested negative for serum anti-GBM antibodies. Although rare, anti-GBM antibody disease should be considered in the differential diagnosis in patients with life-threatening pulmonary haemorrhage due to isolated diffuse alveolar haemorrhage. Enzyme-linked-immunosorbent assay (ELISA) testing for anti-GBM antibodies in anti-GBM antibody disease can give false-negative results. A negative serum anti-GBM antibody test is therefore insufficient to exclude the diagnosis. Thus, a kidney or lung biopsy should be considered in any case with a high clinical suspicion but negative anti-GBM antibody test to confirm or rule out the diagnosis., Learning Points: Diffuse alveolar haemorrhage (DAH) is a life-threatening disorder caused by severe damage due to injury or inflammation of the alveolar-capillary basement membrane.Anti-GBM antibody disease is a rare autoimmune disorder with circulating autoantibodies directed against the alpha-3 chain[Q2] of type VI collagen of the glomerular and/or alveolar basement membrane which may result in oliguric acute kidney failure due to rapidly progressive glomerulonephritis with or without DAH (commonly referred to as Goodpasture's syndrome).A kidney or lung biopsy should be considered to confirm or rule out the diagnosis if there is a high clinical suspicion but the anti-GBM antibody test is negative; prompt diagnosis and initiation of plasmapheresis, cyclophosphamide and prednisone therapy is essential., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Shigella toxin-producing Escherichia coli (STEC) is well known for its complications such as haemolytic uraemic syndrome (HUS), but neurological symptoms have also been reported. While most cases of infection with STEC occur with concurrent HUS, we describe a patient with severe neurological symptoms in the absence of HUS., Learning Points: Shigella toxin producing Escherichia coli (STEC) are bacteria that cause haemorrhagic colitis.Generally, infections with STEC occur with a concurrent haemolytic uraemic syndrome (HUS).However, infections with STEC can occur with neurological symptoms without HUS., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Nowadays the development of a gastro-colic fistula is usually due to malignant disease in the gastro-intestinal tract. The symptoms can vary extensively and establishing the diagnosis quite challenging. We describe the case of a gastro-colic fistula with a complicated course and review the literature., (Copyright© Acta Chirurgica Belgica.)

A pregnant woman presented to a local hospital with abdominal pain and hemorrhagic shock. Emergency caesarean section ruled out an obstetric cause and revealed a large mass, interpreted as a hematoma, with active bleeding of unknown origin. Because of her poor clinical condition, the patient was admitted to our hospital. Computed tomographic findings were suspicious for bleeding originating from the splenic artery. Laparotomy confirmed the presence of a ruptured splenic artery. A splenic artery aneurysm-a relatively well known entity during pregnancy-was absent. Hemostasis was achieved by clipping the artery. A large pancreatic cystic mass, which was misinterpreted earlier as a hematoma, was surgically removed. The pathologic examination revealed a pancreatic lymphangioma, an uncommon benign tumor. The ruptured splenic artery was presumably related to the pancreatic lymphangioma and vascular changes caused by pregnancy. A splenic artery rupture in co-occurrence of a pancreatic lymphangioma is a unique presentation which has not been reported previously., (Copyright © 2013 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

A 29-year-old male marine presented with acute dyspnea and abdominal discomfort. The complaints were caused by a diaphragmatic rupture with an intrathoracic stomach and spleen probably due to an explosion during a military mission a year earlier. Subsequent operative intervention was initiated.

Background: For the treatment of depression in diabetes patients, it is important that depression is recognized at an early stage. A screening method for depression is the patient health questionnaire (PHQ-9). The aim of this study is to validate the 9-item Patient Health Questionnaire (PHQ-9) as a screening instrument for depression in diabetes patients in outpatient clinics., Methods: 197 diabetes patients from outpatient clinics in the Netherlands filled in the PHQ-9. Within 2 weeks they were approached for an interview with the Mini Neuropsychiatric Interview. DSM-IV diagnoses of Major Depressive Disorder (MDD) were the criterion for which the sensitivity, specificity, positive- and negative predictive values and Receiver Operator Curves (ROC) for the PHQ-9 were calculated., Results: The cut-off point of a summed score of 12 on the PHQ-9 resulted in a sensitivity of 75.7% and a specificity of 80.0%. Predictive values for negative and positive test results were respectively 93.4% and 46.7%. The ROC showed an area under the curve of 0.77., Conclusions: The PHQ-9 proved to be an efficient and well-received screening instrument for MDD in this sample of diabetes patients in a specialized outpatient clinic. The higher cut-off point of 12 that was needed and somewhat lower sensitivity than had been reported elsewhere may be due to the fact that the patients from a specialized diabetes clinic have more severe pathology and more complications, which could be recognized by the PHQ-9 as depression symptoms, while instead being diabetes symptoms.

Struma ovarii is the presence of thyroid tissue as the major cellular component in an ovarian tumour. Papillary carcinoma in struma ovarii is exceptionally rare. We report a case of papillary carcinoma in struma ovarii in a postmenopausal 51-year-old female who initially presented clinically with hyperthyroidism. Serology, however, did not confirm hyperthyroidism. During a re-admission to our hospital later that year she appeared to have had periods of postmenopausal vaginal haemorrhage. An abdominal mass was located by radiography and pathological investigation revealed a papillary carcinoma in struma ovarii. Some striking features of this unusual presentation of importance to the internal medicine physician are discussed.

A 68-year-old woman presented at the Casualty Department due to collapse, anaemia, fatigue and progressive dyspnoea. She suffered from melena, indicative of a haemorrhage in the upper gastrointestinal tract. Gastroduodenoscopy revealed the presence of a polyp in the duodenum, which was endoscopically resected. Pathological investigation demonstrated that the polyp was a Brunner's adenoma, i.e. a circumscript benign submucosal nodular hyperplasia of the Brunner's glands.

Objective: In recent years, there has been an ongoing discussion on the relationship between diabetes and driving. As driving performance will inevitably decline at lower levels of glycemia, patients' decisions concerning driving or taking corrective action when hypoglycemia occurs immediately before or during driving seems paramount., Research Design and Methods: Twenty-four type 1 diabetic patients with normal awareness of hypoglycemia (T1Norm group), 21 type 1 diabetic patients with impaired awareness of hypoglycemia (T1Imp group), and 20 type 2 diabetic patients with normal awareness of hypoglycemia (T2 group) were studied. They were asked whether they felt hypoglycemic and whether they would currently drive during experimental euglycemia (5.0 mmol/l) and hypoglycemia (2.7 mmol/l)., Results: In the T1Norm group, 1 patient (4.2%) decided to drive during hypoglycemia. In the T1Imp group, 9 patients (42.9%) said they would drive in the hypoglycemic condition. In the T2 group, 5 patients (25%) would drive. This was more frequently the case for patients on oral hypoglycemic agents (chi2 = 4.44; P = 0.04). No effect of sex (chi2 = 0.78; P = 0.38) or age (chi2 = 0.22; P = 0.64) was noted., Conclusions: Patients with type 1 diabetes and impaired awareness of hypoglycemia frequently decided to drive while hypoglycemic, whereas patients with type 1 diabetes and normal awareness of hypoglycemia appeared to make safe decisions concerning hypoglycemia and driving. Strikingly, patients with type 2 diabetes and normal hypoglycemia awareness frequently made potentially dangerous decisions as well, particularly when using oral hypoglycemic agents. Therefore, early, clear, and consistent education is imperative.

The prevention of type 2 diabetes mellitus (DM2) is a major health issue. The DREAM trial is a multinational, multicentre, prospective double-blind study of 5269 patients with an increased risk of developing diabetes. The results show that treatment with rosiglitazone reduces the risk of developing diabetes in this relatively healthy population. The success is achieved at the expense of side effects such as increased weight gain and a higher incidence of non-fatal congestive heart failure. The DREAM trial provides interesting data that may have major implications, but at the same time raises a number of questions that need to be addressed. The ADOPT study shows the benefits of rosiglitazone over glyburide in de novo DM2.

A 42-year-old man was transferred to the Emergency Department after his friends had found him unresponsive and confused in his room. He had been experiencing upper abdominal complaints for a period of several months. He had taken large amounts of a calcium carbonate/magnesium subcarbonate preparation (Rennie) and had consumed at least 3 litres of dairy products per day. His behaviour was reported as being more and more abnormal during the previous few weeks. On admission he was confused and agitated and had involuntary movements of his limbs. Laboratory investigation indicated a triple acid base disorder, i.e. metabolic alkalosis, respiratory alkalosis and high anion gap metabolic acidosis, with severe dehydration. The metabolic alkalosis was caused by the intake of large amounts of dairy and antacids: milk-alkali syndrome. The metabolic acidosis was the result of hypovolaemia and pre-renal renal failure and the respiratory alkalosis was caused by hyperventilation due to the organic psychosyndrome. The patient was treated with volume expansion by isotonic saline and the administration of potassium and he was sedated with low-dose midazolam, which led to a full respiratory compensation of the metabolic alkalosis. A few days following admission, both the plasma calcium concentration and renal function returned to normal; the acid-base disorder completely normalized and the organic psychosyndrome disappeared. On gastroduodenoscopy a gastric ulcer was found; biopsies revealed a signet ring cell adenocarcinoma of the stomach.

A 76-year-old man presented with diffuse progressive abdominal pain. He had undergone endoscopic retrograde pancreaticocholangiography (ERCP) 5 weeks earlier for jaundice and increased levels of liver enzymes. A dilated biliary duct with multiple concrements had been seen, and a plastic endoprosthesis was placed. During a follow-up ERCP the stent was not found, and the obstruction was still present. Another stent was placed. Abdominal x-ray revealed migration of the first endoprosthesis to the distal jejunum and signs of ileus and free gas. CT showed that the stent was stuck in a perforated diverticulum of the sigmoid, surrounded by an abscess mass. The stent was removed by laparotomy, the perforation was closed, and a double-loop stoma was made. Two weeks after initial recovery, abdominal pain recurred. CT revealed a second dislocated stent with a perforation of the jejunum. Laparotomy was performed again with removal of the stent and repair of the perforation. Migration is a known complication of biliary endoprosthesis placement, and should be considered in cases of abdominal pain after ERCP. Perforations rarely occur and mostly affect areas of the bowel that are fixed or that present obstacles to normal elimination. Two perforations within a short period of time is an extremely rare complication of migration.

Background: Both in research and in various clinical situations, prolonged euglycaemia can be desirable. In recent years, its benefit in (critically) ill patients and patients with acute myocardial infarction has been established. The objective of this study was to assess safety and efficacy of a practical, bodyweight-dependent algorithm to establish euglycaemia in both lean and obese patients with type 1 and type 2 diabetes., Methods: In 43 patients with type 1 diabetes and 17 patients with type 2 diabetes insulin were infused overnight to establish euglycaemia. Plasma glucose concentration was determined at 45 min intervals, and the insulin infusion rate was altered according to the algorithm., Results: Baseline plasma glucose concentrations were 13.1+/- 4.4 and 12.7 +/- 4.0 mmol/l in type 1 and type 2 diabetic patients, respectively. In both groups mean plasma glucose was reduced below 8.0 mmol/l within 3 h, and averaged 7.4 +/- 1.4 and 7.2 +/- 1.0 mmol/l (P = 0.11) over the next 7 h. Five (11.6%) patients with type 1 diabetes required administration of glucose because plasma glucose concentrations fell below 4.4 mmol/l. Consequently, type 1 diabetic patients were hypoglycaemic during 0.89% of the total study period. The lowest plasma glucose recorded was 3.9 mmol/l. In the type 2 diabetic patients the lowest plasma glucose was 5.5 mmol/l and no glucose administration was required for near-hypoglycaemia. The algorithm was equally effective in both lean and obese patients., Conclusions: Euglycaemia was established simply, swiftly and safely during the study period with the practical weight-based algorithm used in this study, in both lean and obese type 1 and type 2 diabetic patients, with a very low rate of mild hypoglycaemia. The algorithm is applicable in research and various several clinical settings. Its validity for a prolonged period of time and in critically ill patients needs to be further evaluated.

The lungs constitute an attractive route for the administration of insulin in view of their large surface area and the permeability for proteins. Inhaled insulin may greatly reduce the daily nuisance of subcutaneous injections for millions of patients. The acceptance of insulin therapy may therefore be increased, so that better metabolic control can be achieved. For optimal efficacy it is essential that the insulin be precipitated in the alveoli and it is precisely the reproducibility of this process that is variable and dependent upon a variety of factors. Thus, the properties of the particles, technique of respiration, administration system and the presence of pulmonary disease (smoking) all play a role. The pharmacokinetics make inhaled insulin suitable for preprandial administration: the absorption is very rapid, so that it can be taken a very short time before meals. The duration of action, however, is short, so that the use of long-acting insulin usually remains necessary. The biological availability of inhaled insulin is < 20%, so that the required dose is larger. The long-term effects of the intra-alveolar administration of insulin and its immunological consequences are still insufficiently clear, although no permanent negative effects have been demonstrated so far. Partly in view of the favourable pharmacodynamic properties, the use of inhaled insulin is an attractive therapeutic option, not only for the group of patients with a fear of injections but for all diabetics that require insulin therapy.

A 37-year-old man in a status epilepticus due to meningitis was admitted to Intensive Care because of respiratory insufficiency. Spinal fluid culture yielded Streptococcus salivarius. Despite extensive diagnostics, the source of this bacterium could not be found. However, the patient had recently undergone spinal anaesthesia for surgery on a toe ulcer, from which other bacteria were cultured. The patient died 2 weeks after admission with a picture of multiple organ failure. Bacterial meningitis following spinal anaesthesia may be the result of impairment of the blood-brain barrier due to a sudden drop of spinal fluid pressure during the puncture, or of the introduction of bacteria from the hair follicles or from a haematoma caused by the needle or the introducer. Hygienic measures and a proper technique when performing regional anaesthesia are important in preventing the dissemination of bacteria.

Objective: We aimed to assess the accuracy of the HemoCue Beta-glucose analyzer (HemoCue) and its correlation with the Yellow Springs Instrument (YSI 2300 STAT; YSI) glucose oxidase analyzer, in particular for hypoglycemic values., Design and Methods: Samples were taken from 24 volunteers during hyperinsulinemic glucose clamp studies. Glucose concentrations were determined immediately with the HemoCue in whole blood and with the YSI in plasma from the same sample. After correction for the difference between whole blood and plasma, the paired plasma glucose concentrations were analyzed with various statistical methods., Results: A total of 500 paired glucose values were obtained, 209 of which were in the hypoglycemic range. Mean+/-s.e. values were 4.85+/-0.004 mmol/l for the HemoCue (range 1.87-16.17) and 4.81+/-0.004 mmol/l for the YSI (range 1.88-15.00; P = 0.80). In the hypoglycemic region, values were 3.26+/-0.004 mmol/l for the HemoCue (range 1.87-5.17) and 3.22+/-0.003 mmol/l for the YSI (range 1.88-4.20; P = 0.59). Regression analyses were HemoCue = 1.019(YSI) -0.0577 mmol/l, with r = 0.9787 for all values; for hypoglycemic values the HemoCue = 1.1169(YSI) -0.3393 mmol/l, with r = 0.8798. Using Altman's residual plot, the difference was 0.03+/-0.0009 mmol/l, with 18 (3.6%) paired values outside the 95% limits of agreement (-0.82 to 0.89 mmol/l). In the hypoglycemic range, the difference was 0.04+/-0.001 mmol/l, with six (2.9%) values outside the 95% limits of agreement (-0.71 to 0.79 mmol/l). In error grid analysis, one value was in zone D (0.2%) and five values (1%) were in zone B; 98.8% were within zone A., Conclusions: Determination of glucose with the HemoCue system had very good correlation with the YSI system in a broad range of glycemia and also for hypoglycemic values. We believe that these methods can be used interchangeably for research and clinical purposes in adults.

Objective: To determine whether intravenous infusion of either human albumin or hydroxyethyl-starch (HES) in hypo-albuminemic critically ill may lead to an increase in colloid osmotic pressure and to a better clinical outcome, i.e. lower mortality and fewer complications, compared to fluid replacement with normal saline., Design: Prospective, randomized controlled clinical trial during 72 hours in 61 consecutively admitted severely ill patients. Randomisation took place by sealed envelope, kept outside of the hospital., Setting: Intensive care unit of the Twenteborg Hospital, Almelo, The Netherlands., Subjects: Sixty-three severely ill, hypo-albuminemic patients were selected; 27 patients had severe sepsis and 36 were post-surgical patients with SIRS. Two patients died shortly after randomization, 15 patients received human albumin, 15 HES 500 and 15 HES 1000 ml, and 16 saline., Interventions: The patients were randomized to receive 300 ml human albumin (20%) per day, or 1000 ml normal saline per day, or 500 ml or 1000 ml HES per day, all for 72 hours., Main Outcome Measures: The primary outcome was plasma colloid osmotic pressure (COP). Secondary endpoints were fluid balance and the development of pulmonary edema., Results: Administration of human albumin was effective in raising COP (P<0.001 on day 2 and day 3, compared to saline and HES). Neither fluid balances nor the development of peripheral or pulmonary edema were different between the groups. Mortality as well as length of stay at ICU were slightly higher in the group receiving human albumin, although not statistically significant., Conclusion: Raising colloid osmotic pressure with human albumin in hypoalbuminemic patients is not associated with improvement of the clinical outcome.

Objective: We tested the hypothesis that impaired tissue sensitivity to catecholamines contributes to hypoglycemia unawareness in subjects with type 1 diabetes., Research Design and Methods: A total of 21 subjects with type 1 diabetes underwent a standardized insulin infusion protocol to produce a stepwise decrease in plasma glucose to 45-min plateaus of 4.3, 3.6, 3.0, and 2.3 mmol/l. Glycemic thresholds, maximum responses for adrenergic and neuroglycopenic symptoms, and counterregulatory hormones were determined. Patients were classified as hypoglycemia unaware if the initiation of adrenergic symptoms occurred at a plasma glucose level 2 SD below that of nondiabetic volunteers. beta-Adrenergic sensitivity was measured as the dose of isoproterenol required to produce an increment in heart rate of 25 beats per minute above baseline (I25) in resting subjects., Results: Subjects with type 1 diabetes and hypoglycemia unawareness experienced the onset of adrenergic symptoms at a lower plasma glucose level than did those with awareness (2.5+/-0.1 vs. 3.7+/-0.1 mmol/l, P < 0.001), whereas neuroglycopenic symptoms occurred at similar glucose levels (2.7+/-0.2 vs. 2.8+/- 0.1 mmol/l). The plasma glucose levels for counterregulatory hormone secretion (epinephrine 2.9+/-0.2 vs. 4.1+/-0.2 mmol/l; norepinephrine 2.7+/-0.1 vs. 3.2+/-0.2 mmol/l; cortisol 2.5+/-0.2 vs. 3.3+/-0.2 mmol/l, P < 0.01) were also lower in subjects with unawareness. The maximal epinephrine (1,954+/-486 vs. 5,332+/- 1,059 pmol/l, P < 0.01), norepinephrine (0.73 +/- 0.14 vs. 1.47+/-0.21 nmol/l, P = 0.04), and cortisol (276+/-110 vs. 579+/-83 nmol/l, P < 0.01) responses were reduced in the unaware group. I25 was greater in unaware subjects than in subjects without unawareness (1.5+/-0.3 vs. 0.8+/-0.2 microg), where I25 was not different from that of controls (0.8 +/-0.2 microg)., Conclusions: We conclude that subjects with type 1 diabetes and hypoglycemia unawareness have reduced beta-adrenergic sensitivity, which may contribute to their impaired adrenergic warning symptoms during hypoglycemia.

Disturbances in insulin secretion and insulin action are both involved in the pathophysiology of type 2 (or non-insulin-dependent) diabetes mellitus. The newly developed sulfonylurea (SU) derivative glimepiride has a marked insulin secretory effect both in vitro and in vivo, and is capable of increasing plasma insulin levels with approximately 50% in type 2 diabetes subjects. Glimepiride improves metabolic control comparable but not superior to other (second generation) SU derivatives. Although it has been advocated for once-daily use, maximum effect is presumably achieved by twice-daily dosing. One of the most important side-effects of SU remains hypoglycemia in some patients, which may last for several hours. Although there is some indication that the use of glimepiride leads to fewer hypoglycemic episodes than glibenclamide, the differences reported sofar are not statistically significant.

Electrical shocks commonly cause widespread acute and delayed tissue damage. Cardiac arrhythmias and respiratory arrest are the most life-threatening complications in the acute phase. Prediction of outcome after cardiopulmonary resuscitation is usually based on neurological findings compatible with anoxic encephalopathy. This report describes a case of electrocution followed by cardiopulmonary resuscitation. Although neurological signs on admission pointed towards severe brain injury, the patient fully recovered and was able to resume the level of cognitive functioning prior to the accident.

At present, no clear evidence is available that, as a group, patients with diabetes mellitus are at increased risk of becoming involved in traffic accidents. However, accidents as a consequence of hypoglycaemia do occur, and the percentage of accidents in patients with insulin-dependent diabetes mellitus resulting from hypoglycaemia has been estimated at 5.2%. A recent study using computer-stimulation techniques showed that during moderate hypoglycaemia (2.6 mmol/l) driving performance deteriorated significantly. Only one third of these subject were aware of it. Surprisingly, only half of them stated that they would not to drive under such circumstances. Unawareness of hypoglycaemia forms a major risk factor. With the present efforts to improve metabolic control with intensive insulin therapies the incidence of unawareness and therefore of severe hypoglycaemic reactions is increasing. With intensive education programs such as blood glucose awareness training (BGAT) introduced by Cox et al. patients learn to estimate blood glucose concentrations and specifically to detect hypoglycaemia at an early stage. The first studies show that after BGAT the incidence of hypoglycaemia decreases. Interestingly, after BGAT, patients were less frequently involved in traffic accidents (crash rates per 1,000,000 miles 6.8 vs. 29.8, p = 0.01). Therefore, although many questions remain to be answered, BGAT has proved beneficial in reducing hypoglycaemic episodes and in reducing traffic accidents.

Although sulfonylureas (SU) are widely used in the management of patients with non-insulin-dependent diabetes mellitus (NIDDM), there is still debate about their mechanism of action on the pancreatic beta cell. It is unclear whether the effect of SU on insulin release is additive to the effect of glucose, or whether SU act by increasing pancreatic beta-cell sensitivity to glucose (a shift in the dose-response curve of glucose-stimulated insulin release without a change in maximum release). To address this issue, we assessed the influence of the SU gliclazide on glucose-stimulated insulin release in eight healthy male volunteers. Sixty-minute hyperglycemic glucose clamps (blood glucose levels: 8 mmol/L, a submaximal stimulus; and 32 mmol/L, a maximally stimulating concentration) were performed with and without prior oral administration of gliclazide (80 mg) 30 minutes before the glucose clamp. Mean plasma C-peptide increment at 5 minutes (first-phase secretion) obtained during the 8-mmol/L hyperglycemic clamp, was higher on the gliclazide study day than on the control day (1.07 +/- 0.10 v 0.88 +/- 0.10 mmol/L, P less than .05), whereas no difference in plasma C-peptide response was observed during the 32-mmol/L hyperglycemic clamp. Mean plasma C-peptide increment obtained at the end 60 minutes; (second-phase secretion) of the 8-mmol/L hyperglycemic clamps was higher on the gliclazide study day than on the control day (1.36 +/- 0.13 v 1.09 +/- 0.09 mmol/L, P less than .02). No difference was observed in plasma C-peptide response at the end of the 32-mmol/L hyperglycemic glucose clamps.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Sulphonylurea derivatives are commonly used in the treatment of non-insulin-dependent diabetes mellitus. It is, however, unclear whether the hypoglycaemic effect of sulphonylurea derivatives is additive to the effect of glucose, or whether sulphonylurea derivatives act by increasing B-cell glucose sensitivity. 2. We assessed the effect of gliclazide on glucose-stimulated insulin secretion in eight healthy volunteers. Sixty minute hyperglycaemic glucose clamps (blood glucose levels of 8, 11 and 32 mmol/l) were performed, with and without prior administration of gliclazide (80 mg) 90 min before the glucose clamp. 3. Dose-response characteristics were assessed with a modified Michaelis-Menten equation. The Vmax. (maximal B-cell responsiveness) was not significantly changed (1.5 +/- 0.1 versus 1.3 +/- 0.2 and 5.0 +/- 0.5 versus 4.8 +/- 0.5 mmol/l for the first- and second-phase insulin secretion, respectively), whereas the ED50 (half-maximally stimulating blood glucose concentration) was significantly decreased by gliclazide for first-phase insulin secretion (7.6 +/- 0.3 versus 9.1 +/- 0.6 mmol/l) but not for second-phase insulin secretion (12.0 +/- 0.5 versus 12.3 +/- 0.5 mmol/l). 4. We conclude that gliclazide indeed leads to a shift to the left of the dose-response curve of first-phase insulin release in vivo without a change in Vmax, which indicates an apparent enhancement of B-cell glucose sensitivity.

In order to determine the influence of acute inhibition of prostaglandin synthesis on insulin release in man, the influence of lysine acetyl-salicylate (0.9 g) on glucose- and arginine-stimulated insulin release was studied in eight volunteers. No significant differences were found in plasma C-peptide levels between the salicylate and the control study days during administration of arginine (0.5 g/kg; 30 min) nor during a hyperglycemic clamp (glucose level 17 mMol/L; 60 minutes). These studies indicate that acute administration of salicylate does not change insulin release in man.

A family is described in which both a mother and an infertile daughter had premature menopause at the ages of 31 and 28 years, respectively. Initially, an extensive investigation revealed no apparent cause for their conditions. However, when cytogenetic analysis in the daughter was performed, a terminal deletion in the long arm of one of the X-chromosomes was found. The karyotype was: 46,Xdel(X),(q25-qter). Chromosomal investigation in the mother showed an identical deletion. The karyotype of the patient's 35-year-old sister is normal. She has a normal menstrual cycle and two normal children. The presence of such familial cases suggests that chromosomal investigation should be considered in young women with oligomenorrhea, especially those whose mothers have experienced a premature menopause.

Glucose potentiates arginine-induced insulin release. We investigated the dose-response characteristics for both phases of glucose-induced insulin release in normal man, and studied the influence of hyperglycemia on arginine-induced insulin secretion. Dose-response curves of plasma C-peptide increments achieved during 60-minute hyperglycemia clamps (7, 11, 17, 24, and 32 mmol/L) with and without a primed continuous infusion of arginine (infusion rate, 15 mg/kg/min) were analyzed with a modified Michaelis-Menten equation. The ED50 (half-maximally stimulating blood glucose concentration) of first-phase insulin release (determined from plasma C-peptide increments at 5 minutes) was significantly lower than the ED50 for the second phase (60 minutes; 8.4 +/- 0.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .002). Combined glucose-arginine stimulation significantly increased insulin release. Vmax of both phases of glucose-arginine-stimulated insulin release were positively correlated (r = .75, P less than .05). The ED50 of the influence of glucose on first-phase arginine-induced insulin release was significantly lower than the ED50 for the second phase (9.0 +/- 1.1 v 12.7 +/- 1.0 mmol/L, respectively, P less than .02). For each insulin secretion phase separately, the ED50 for the influence of hyperglycemia on arginine-induced insulin release were not significantly different from the ED50 for glucose-induced insulin secretion (without arginine). When dose-response curves of plasma insulin increments were analyzed with the same equation, the ED50 of second-phase glucose-induced plasma insulin increments was significantly higher than the ED50 assessed from the plasma C-peptide increments (21.6 +/- 2.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

We analyzed the relapse rates of hyperthyroidism and prevalence rates of hypothyroidism after partial thyroidectomy and radio-iodine therapy in patients with Graves' disease and toxic multinodular goitre. In achieving euthyroidism, partial thyroidectomy was more effective in patients with Graves' disease (P less than 0.02). In patients with toxic multinodular goitre, radio-iodine therapy was more successful (P less than 0.05). Relapse of hyperthyroidism occurred more often in the radio-iodine group (P less than 0.02), mainly in patients with Graves' disease, and was seen sooner after radio-iodine therapy than after surgery (P less than 0.0001). Patients with toxic multinodular goitre, developed hypothyroidism more often after partial thyroidectomy than after 131I (P less than 0.01). In contrast, in patients with Graves' disease, hypothyroidism occurred more often after radio-iodine therapy than in the toxic multinodular goitre group (P less than 0.02). We conclude that the cause of hyperthyroidism strongly influences the efficacy of the therapeutic regimen.