Anti-phospholipid antibodies in diabetes mellitus.

The presence of autoantibodies to phospholipids may be associated with various pathological disorders; diabetes could be one of them because of the changes occurring in lipid metabolism but there are only few reports examining this question, and they are not always leading to the same conclusions because of the differences in the procedures or in the phospholipids tested. We carried out a systematic comparative study of diabetic serum antibody binding to all phospholipids, anionic and zwitterionic, by a quantitative ELISA. The implication of the hydrophobic moiety of the lipids was also studied: the presence of autoantibodies to the fatty acyl chains was investigated. Our results show the presence of anti-phospholipid antibodies in diabetic sera, particularly anti-phosphatidylinositol and anti-phosphatidylcholine which have never been tested before, and appear to be associated with macroangiopathic complications. The antigenic epitopes are mainly the polar heads as no antibody binding to the hydrophobic moiety was observed. We discuss the relation of those antibodies to the angiopathic complications and to the direct effects of hyperglycemia on lipid antigenicity.     

Diabetes as a result of atypical anti-psychotic drugs--a report of three cases.

AIMS: Atypical anti-psychotic drugs (APDs) are widely used in psychotic disorders refractory to conventional neuroleptic agents. RESULTS: Three cases of new-onset diabetes are reported in Caucasian men who were on clozapine (one) or olanzapine (two) for 3-6 months. They had a distinct presentation: weight loss, ketosis (one ketoacidosis), severe hyperglycaemia requiring insulin therapy, and relative insulin deficiency as reflected by glucagon stimulatory tests. In all cases, insulin was stopped within 1 month after the APD was discontinued. CONCLUSIONS: Novel APDs not only induce diabetes as a result of weight gain in predisposed patients, but can also lead to a reversible state of insulin deficiency, and sometimes ketoacidosis.     

Occult Cushing's syndrome in type-2 diabetes

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.     

Effect of metformin on fibrinolytic parameters in insulin-treated, type 2 diabetic patients

OBJECTIVE: In the present study, we measured fibrinolytic parameters, including PAI-1 antigen and activity in a group of type 2 diabetic patients in secondary oral anti-diabetic failure treated with insulin alone or with insulin plus metformin. RESEARCH DESIGN AND METHODS: 12 type 2 diabetic patients in secondary oral anti-diabetic failure were randomly allocated into two groups receiving insulin alone or insulin plus metformin 1000 mg twice a day; six weeks later, the treatments were swapped over. At the end of each treatment period, blood samples were withdrawn for metabolic and fibrinolytic analysis. RESULTS: There were no significant differences in fasting blood glucose, fructosamine or fibrinogen; LDL cholesterol, PAI-1 antigen and activity, insulin needs were reduced by the inulin plus metformin regimen (LDL cholesterol: 1.59 +/- 0.62 versus 1.28 +/- 0.5 mmol/l, PAI-1 antigen: 28.3 +/- 17.4 versus 23.9 +/- 18 ng/ml, PAI-1 activity: 23.8 +/- 9.6 versus 21.9 +/- 10 IU/ml, insulin needs: 64 +/- 18 versus 52 +/- 15 U/day (p<0.05). CONCLUSION: In type 2 diabetic patients with secondary oral treatment failure, insulin alone controlled blood glucose but had no effect on the levels of PAI-1; addition of metformin improved the fibrinolytic parameters.     

Familial non-medullary thyroid carcinoma: pathology review in 27 affected cases from 13 French families

BACKGROUND AND OBJECTIVES: When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC. PATIENTS AND METHODS: Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed. RESULTS: Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous. CONCLUSION: Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue.     

Composition of insulin-induced body weight gain in diabetic patients: a bio-impedance study

Although insulin is a well-known cause of body weight gain, it is not clear whether it is due to the accumulation of fat or lean mass. We performed a 3 months Body-Impedance Analysis follow-up in 72 diabetic patients in a wide range of insulin indications: insulin introduction in young inaugural type 1 diabetics (n = 12), late-onset type 1 (n = 12), type 2 affected by intercurrent diseases (n = 12) or microangiopathic complications (n = 12), type 2 with failure of oral antidiabetic agents (n = 12), and insulin withdrawal in type 2 (n = 12). In type 1 patients, insulin led to the most important weight gain, but it was fat-free, with a major benefit on HbA1C. Type 2 patients affected by intercurrent diseases or microangiopathic complications had a mild, also fat-free weight gain, with a clear benefit on HbA1C. In type 2 patients with failure of oral agents, HbA1C declined less, weight gain was intermedia, but predominantly fat, mirrored by a predominant fat loss in type 2 patients whose insulin was stopped (without significant change in HbA1C). Both fat and lean mass contributed to insulin-induced body weight gain, but a significant negative relationship existed between their respective evolution in our patients (r = -0.23, p < 0.05 by linear regression analysis between delta fat mass and delta lean mass). Insulin-induced body weight gain is not univocal: insulin restaures or protects lean mass in its less controversial indications, whereas it leads to fat accumulation in type 2 patients with isolated failure of oral agents.     

Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.