Plasma C-peptide levels and clinical remissions in recent-onset type I diabetic patients treated with cyclosporin A and insulin

Remission from insulin dependency in insulin-treated recent-onset type I (insulin-dependent) diabetic patients can result from a partial recovery of insulin secretion, an improvement in tissue sensitivity to insulin, or both. The same hypothesis must be analyzed when remission occurs in cyclosporin A (CsA)-treated patients. In this study, plasma C-peptide levels were serially measured in the basal state and after stimulation in 219 recent-onset type I diabetic patients; 129 received CsA, and all patients were similarly monitored and insulin treated. The results were analyzed in view of the occurrence of remission. Remission was defined as good metabolic control in the absence of hypoglycemic treatment for greater than or equal to 1 mo. Remission occurred in 44% of the CsA-treated group and lasted for mean +/- SE 10.0 +/- 0.9 mo vs. 21.6% in the non-CsA-treated group with a duration of 4.4 +/- 0.8 mo. Plasma C-peptide levels were initially dramatically lower than normal in both groups in the basal and stimulated states. C-peptide levels increased significantly later, at 3 and 6 mo, in both groups. C-peptide values were proportional to the rates of remission in both groups. In the non-CsA-treated group, C-peptide levels later decreased, and these patients inexorably relapsed to insulin dependency. In contrast, in the CsA-treated group, the initial recovery in insulin secretory capacity was maintained over the 18-24 mo of the study. Furthermore, higher remission rates and longer-lasting remission were obtained in patients who reached higher C-peptide levels at the 3rd mo of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a chemiluminometric immunoassay for detection ofChlamydia trachomatis in the urine of male and female patients

A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection ofChlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation ofChlamydia trachomatis was 23.5 % in men, nearly 80 % of whom had symptoms of urethritis, and 8.3 % in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8 % and 70 %, a specificity of 97 % and 95 %, a positive predictive value of 89.4 % and 58.3 %, and a negative predictive value of 94.3 % and 97.2 %. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection ofChlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population.     

Health and functional status of adult recipients 1 year after allogeneic haematopoietic stem cell transplantation

Increasing numbers of patients are surviving after allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, a number of late complications have been described but few data on the risk factors of these long-term effects of SCT are available. We report the analysis on 105 adult patients, surviving free of haematological disease at a median time of 15 months after SCT. At the time of screening, 52% had returned to work, general health status was normal in 67% and 47% were sexually active. Female patient gender odds ratio (OR) 2.9 (P = 0.01) and age > 25 years (OR = 3.2, P = 0.02) were associated with non-return to work. Decreased general status was associated with chronic graft-versus-host disease (GvHD) (OR = 3.2, P = 0.009) and irradiation (OR = 3.6, P = 0.004). Sexual inactivity was associated with younger age (OR = 7.0, P = 0.0002) and chronic GvHD (OR = 3.3, P = 0.006). Risk factors for altered pulmonary function tests included previous smoking habits, irradiation and chronic GvHD. Obstructive lung disease was associated with a previous history of asthma. Sicca syndrome and conjunctivitis were increased in patients with previous acute GvHD and cataracts were less frequent in patients with aplastic anaemia. Persistent impaired hair re-growth was less frequent in patients who received irradiation (OR = 0.18, P = 0.002) but increased in patients with previous acute GvHD (OR = 5.3, P = 0.007). Microalbuminuria was more frequent in irradiated patients (OR = 9.4, P = 0.05). Raised cholesterol was associated with age (OR = 20.8, P < 0.001), previous acute GvHD (OR = 4.7, P = 0.03), steroid use (OR = 6.3, P = 0.001) and familial hypercholesterolaemia (OR = 4.4, P = 0.04). Decreased bone density was associated with chronic GvHD (OR = 3.9, P = 0.001). Thus, using routine tests in adult patients we were able to detect significant numbers of-non-symptomatic complications enabling early treatment.     

Adrenal insufficiency and diabetes mellitus secondary to the use of topical corticosteroids for cosmetic purpose

We report a case of symptomatic topical corticosteroid-induced adrenal insufficiency and diabetes in a 46-yr old HIV 1 positive woman of African descent. Topical Betamethasone dipropionate 0.05%-containing creams were used for the purpose of bleaching over a 2 month period prior to the acute episode. She recovered from her acute onset diabetes with ketosis and adrenal insufficiency a few months after withdrawal of corticosteroids. Despite possible discussion about pathophysiology of diabetes because acute-onset remitting diabetes is not rare in patients of African descent, and diabetes may occur in patients taking anti-retroviral treatments, no other cause of a hypothalamo-pituitary-adrenal axis disorder was found. This case suggests that chronic use of high dose topical corticosteroid containing creams should be ruled out in patients presenting with Hypothalamo-Pituitary-Adrenal hypofunction.     

Novel mutations in CYP21 detected in individuals with hyperandrogenism

We studied the functional and structural consequences of two novel missense mutations in CYP21 found in women with hyperandrogenism. The women were predicted to carry mutations by hormonal evaluation, but did not display any of the genotypes commonly associated with congenital adrenal hyperplasia. In one woman the novel mutation V304M was found in homozygous form. After expression in COS-1 cells the mutated enzyme was found to have a residual activity of 46% for conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone compared with the normal enzyme. The V304M variant thus represents the sixth known missense mutation associated with nonclassical disease. A normal degradation pattern for this mutant enzyme indicates that the missense mutation is of functional, rather than structural, importance. The other mutation, G375S, was detected in a young woman with signs of hyperandrogenism, in heterozygous form together with P453S, a mutation known to cause nonclassical congenital adrenal hyperplasia (her genotype was G375S+P453S/wild type). This novel variant almost completely abolished enzyme activity; conversion was 1.6% and 0.7% of normal for 17-hydroxyprogesterone and progesterone, respectively. These results underline the importance of genetic evaluation and counseling in hyperandrogenic women who are predicted to carry congenital adrenal hyperplasia-causing mutations by biochemical tests. It also supports the idea that the heterozygous carrier state for CYP21 mutations can be associated with symptoms of androgen excess in certain susceptible individuals.     

Effects of a single bout of exercise and exercise training on steroid levels in middle-aged type 2 diabetic men: relationship to abdominal adipose tissue distribution and metabolic status

Lower androgen levels have been suggested to be associated with type 2 diabetes and central obesity and are probably involved into the development of atherosclerosis. The present study investigates the effect of acute and chronic exercise on Dehydroepiandrosterone (DHEA) levels in relation to abdominal fat distribution and metabolic status in type 2 diabetes. Twenty weight-stable, middle-aged males with type 2 diabetes were enrolled in the study and participated in a submaximal (VO(2) peak) and moderate (50% VO(2) peak) exercise bout. The subjects were randomly assigned either to a trained or a control group, respectively. Physical training consisted of an 8 week program of aerobic exercise (75% VO(2) peak, 45 min), twice a week and intermittent exercise, once a week, on a bicycle ergometer. Acute exercise significantly increased DHEA and Testosterone (T) levels. Physical training increased VO(2) peak (42%, p <0.001), insulin sensitivity index (K(ITT) ) (57.5%, p <0.02), and basal DHEA levels (36%, p <0.05), and decreased HbA1c (29%, p <0.001), visceral adipose tissue (VAT) (44%, p <0.01) and subcutaneous adipose tissue (SAT) levels (18%, p <0.01). Body weight, BMI and insulin, T levels were not modified. Changes in DHEA levels were not correlated with changes in insulin sensitivity and abdominal fat distribution. In conclusion, exercise training favourably affects DHEA levels independently of improvements of metabolic status and abdominal fat distribution in patients with type 2 diabetes.     

Amelioration of glucose tolerance and correction of reactive hypoglycemias induced by intravenous calcium infusion cannot be explained by modifications in blood glucagon levels

Glucagon is not involved in intravenous calcium-induced improvement in glucose tolerance nor in correction of reactive hypoglycemia. Recent investigations have shown that intravenous (IV) calcium infusion improved blood glucose values in patients with moderately impaired glucose tolerance, and suppressed hypoglycemia in patients with isolated reactive hypoglycemia. The aim of this study was to investigate the possibility that these changes were secondary to calcium induced alterations in glucagon (IRG) secretion. Four groups of subjects were studied: group 1: normal controls (n = 7); group 2: patients with isolated hypoglycemia (n = 9); group 3: patients with impaired glucose tolerance without reactive hypoglycemia (n = 9) and group 4: patients with impaired glucose tolerance and reactive hypoglycemia (n = 10). All patients were submitted in randomized order to two 5 hour oral glucose tolerance tests (OGTT, 75 g glucose), during a simultaneous infusion, either of saline or of calcium (calcium gluconate 36.3 mEq/5 h.), starting 30 minutes before the OGTT. In none of the groups did calcium infusion influence basal plasma IRG. In group 1 and 3, oral glucose significantly suppressed IRG, and during IV calcium infusion this suppression disappeared. In group 2, glucose ingestion resulted in a paradoxical increase in IRG both during saline and during calcium infusion. In group 4, oral glucose induced a significant drop in plasma IRG and a rebound rise during hypoglycemia, results which were unaffected by IV calcium infusion. These data suggest that glucagon is not involved in the alterations of blood glucose profiles during OGTT observed during intravenous calcium infusion.     

Primary gastric plasmacytoma with IgG dysgammaglobulinemia and macrocytic anemia (author's transl)]

The authors report a case of a woman aged 76 years with a single plasmocytoma of the stomach secreting large quantities of a paraprotein of the IgG type with Kappa light chains. A macrocytic anemia due to deficiency of gastric intrinsic factor was also present. This pathological association is extremely rare. About sixty cases of gastric plasmocytoma are been reported in the published literature and their principal characteristics are briefly outlined.     

β- and α-Cell Dysfunctions in Africans With Ketosis-Prone Atypical Diabetes During Near-Normoglycemic Remission

OBJECTIVE

Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.

RESEARCH DESIGN AND METHODS

We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.

RESULTS

Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.

CONCLUSIONS

Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.Ketosis-prone atypical diabetes (KPD) is a frequent specific subtype of diabetes in African Americans and sub-Saharan Africans (1–3). Patients with KPD present at onset with acute hyperglycemia and ketosis or ketoacidosis owing to an insulin secretory deficiency, but autoimmune markers against islet β-cells are absent (4–6). A prolonged insulin-free near-normoglycemic remission phase frequently follows the acute phase after insulin treatment and is associated with a significant recovery of the insulin secretory function (4,7,8). These observations have suggested that the blunting in insulin secretion at disease onset may be due to a functional disorder of β-cells rather than to cell destruction. We previously hypothesized that KPD is a subtype of type 2 diabetes with acute onset at diagnosis as the result of an environmental triggering factor, such as a viral infection, that severely impairs glucose-stimulated insulin secretion and favors ketogenesis (9). KPD patients display insulin resistance at the level of muscles, liver, and adipose tissue during remission (10). However, maximal insulin secretory capacity and surrogates of α-cell mass have not been evaluated, and whether α-cell dysfunction also contributes to the pathophysiology of KPD, as described in type 2 diabetes (11–14) is not known.In the current study, we therefore measured early insulin secretion in response to oral glucose, dose-response insulin secretion to intravenous glucose, and maximum secretory response to arginine combined with glucose (glucose potentiation of arginine-induced insulin secretion) in Africans with KPD during near-normoglycemic remission compared with control subjects of the same ethnic background. Function of α-cells was assessed by measuring glucagon in response to glucose, insulin, and arginine.