PubMed Health⌕ Search

Biomedical subjects

R G Bretzel

Publications and source records attributed to R G Bretzel.

At least 109 records · Page 6Linked to original sources
PubMed1997

Leptin inhibition of insulin secretion from isolated human islets.

Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety, food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic beta-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an "adipo-insular axis" in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas.

Animals↗
PubMed1997

Diabetes in pregnancy.

Women with diabetes in pregnancy can be divided into two groups: women with diabetes diagnosed before pregnancy (pregestational diabetes) and women with glucose intolerance diagnosed during pregnancy (gestational diabetes mellitus). The majority of women with pregestational diabetes have insulin-dependent diabetes mellitus (IDDM), but may also include early-onset non-insulin dependent diabetes mellitus (NIDDM). Gestational diabetes mellitus (GDM) can represent first recognition of IDDM or NIDDM. The expression of each of the forms of diabetes as a clinical disorder represents a complex interaction of genetic and environmental factors. The prevalence of GDM varies between 0.15 and 4% and the prevalence of pre-GDM 0.2-0.4% in European countries [1].

Diabetes Mellitus, Type 1↗
PubMed1997

Protecting the residual renal function: which drugs of choice?

Diabetic nephropathy is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. Proteinuria heralds the clinical nephropathy, and the worsening of proteinuria parallels the progression of renal disease towards chronic renal failure. A large body of evidence has accumulated that emphasizes the role of elevated blood pressure in the progression of renal disease, as well as the clear benefit of antihypertensive treatment. However, the choice of antihypertensive drug to protect renal function was less clear in the past. In earlier studies, a reduction in the rate of progressive renal failure in hypertensive subjects has been shown with diuretics, beta-blockers, and vasodilators. However, there is now increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some calcium antagonists produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive nephroprotective effects. Finally, ACE-inhibitors and calcium antagonists have no adverse effects on glycemic control or lipid levels and may even improve insulin sensitivity. This further promotes these antihypertensives to first-line drugs when treating subjects at risk of metabolic disorders or people with diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effects of antihypertensive drugs on renal function in patients with diabetic nephropathy.

Hypertension occurs about twice as frequently in diabetics as in the general population, with a prevalence of approximately 25% in young patients with insulin-dependent diabetes mellitus (IDDM) and 50% in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). Studies strongly suggest that hypertension is involved in the progression and perhaps the onset of diabetic nephropathy, which is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. A large body of evidence has accumulated that emphasizes the beneficial effects of antihypertensive treatment in reducing proteinuria and preserving renal function in both IDDM and NIDDM. It appeared that angiotensin converting enzyme inhibitors and certain calcium antagonists, notably nondihydropyridine, calcium antagonists, and second-generation dihydropyridine calcium antagonists, produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive effects on reduction in albuminuria and have led to the lowest rate of decline in glomerular filtration rates with the lowest incidence of adverse effects.

Antihypertensive Agents↗
PubMed1997

Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status.

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.

Adolescent↗
PubMed1997

Can we further slow down the progression to end-stage renal disease in diabetic hypertensive patients?

HYPERTENSION AND DIABETES: Hypertension occurs about twice as frequently in diabetics compared with the general population, with a prevalence of approximately 25% in young patients with insulin-dependent diabetes mellitus (IDDM) and 50% in newly diagnosed non-IDDM (NIDDM) patients. Studies strongly suggest that hypertensions is involved in the progression and perhaps the onset of diabetic nephropathy, which is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. TREATMENT: A large body of evidence has accumulated which emphasizes the beneficial effects of antihypertensive treatment in reducing proteinuria and preserving renal function in both IDDM and NIDDM. It appears that angiotensin converting enzyme inhibitors and certain calcium antagonists, notably the non-dihydropyridine type and second-generation dihydropyridine calcium antagonists, produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression in renal failure. These drugs have displayed a nephroprotective capacity beyond their systemic blood pressure-lowering effects, and initial clinical trials with combinations of different antihypertensive drug classes have revealed additive effects in reducing albuminuria together with the lowest rate of decline in glomerular filtration rates with the lowest incidence of adverse effects. AVAILABLE STUDIES: The studies available on antihypertensive treatment in IDDM and NIDDM patients with incipient or overt diabetic nephropathy are mainly prospective. There have also been some preliminary trials with antihypertensive combinations in diabetic patients.

Acute Kidney Injury↗
PubMed1997

Progressive islet graft failure occurs significantly earlier in autoantibody-positive than in autoantibody-negative IDDM recipients of intrahepatic islet allografts.

Alloimmunity has been uncovered to be a cause of graft loss representing a major barrier for clinical islet transplantation, and several studies are designed to evaluate new strategies for immunosuppression to prevent alloimmunity. In contrast, the significance for autoimmune destruction of transplanted beta-cells has remained somewhat controversial. Recently, two case reports based on histological findings have suggested recurrent autoimmune insulitis despite immunosuppressive therapy both in clinical pancreas and in islet transplantation. In the present study, in 23 islet-grafted patients with IDDM receiving standard immunosuppressive therapy, we demonstrate that progressive impairment of islet graft function occurs significantly earlier in those individuals positive for autoantibodies as a typical stigma of diabetes-associated autoimmunity that is well established in the prediabetic periods of IDDM. Intraportal infusion of allogeneic islets was performed in 23 C-peptide-negative IDDM patients, according to the clinical transplantation categories defined as islet after kidney (IAK) or simultaneous islet and kidney (SIK). Complete islet graft failure was defined as the 1st day of permanent C-peptide negativity in the serum (<0.2 ng/ml) and C-peptide negativity in the urine (<2 microg/dl). The median observation period following islet transplantation was 12 months (range 1-50) with a cumulative follow-up of 336 months. Islet cell antibodies (ICAs) and GAD65 antibodies were monitored before and regularly after islet transplantation. Kaplan-Meier survival analysis and log-rank statistics revealed a significant (P < 0.05) difference in cumulative islet graft survival depending on the presence of islet cell and/or GAD65 antibodies. These results strongly suggest that recurrent autoimmunity directed to transplanted beta-cells contributes to islet graft failure despite sustained immunosuppression. For successful clinical islet transplantation in the future, new immunosuppressive therapies are needed to prevent both alloimmunity and autoimmunity.

Adult↗
PubMed1996

Islet cell antibodies and glutamic acid decarboxylase antibodies in patients with insulin-dependent diabetes mellitus undergoing kidney and islet-after-kidney transplantation.

The humoral immune response to islet autoantigens, here defined by the presence of islet cell antibodies (ICA) and glutamic acid decarboxylase (GAD 65) antibodies, was studied in patients with long-term insulin-dependent diabetes mellitus (IDDM) receiving immunosuppressive therapy following kidney and islet-after-kidney transplantation. In a cross-sectional study of 30 kidney-grafted, long-term IDDM patients and 30 matched, nontransplanted IDDM controls, we observed a significant (P<0.05) decrease in ICA positivity by standard immunosuppressive therapy, but not in frequency or index levels of GAD 65 antibodies. Because of this intriguing finding, we investigated, in a pilot study on seven islet-after-kidney transplant recipients, the time course of frequency and levels of ICAs and GAD 65 antibodies relative to islet graft function. Stable islet graft function was seen in the patients with low GAD 65 antibody index levels, whereas rapid islet graft failure occurred in a patient with high GAD 65 antibody index levels prior to transplantation. In addition, GAD 65 autoimmunity reoccurred in one pretransplant antibody-negative patient 2 months after graft failure was noted. In conclusion, these observations suggest that beta-cell autoimmunity directed to GAD 65 can persist despite immunosuppressive therapy and may adversely affect islet graft function, possibly indicating disease recurrence as a major threat to successful clinical islet transplantation.

Adult↗
PubMed1996

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/di) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1 +/- 1.4 mg/kg/ min; P < 0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4 +/- 0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9 +/- 0.5 mg/kg/min in patients without islet function and 5.3 +/- 0.4 mg/kg/min in patients with islet function) with respect to normals (P < 0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.

Adult↗
PubMed1996

GAD 65 antibody but not ICA positivity in adult-onset diabetic patients is associated with early progression to clinical insulin dependency.

Correct classification of diabetic patients in adulthood at the time of diagnosis is often difficult. Some may be initially diagnosed as having non-insulin-dependent diabetes mellitus and be treated with diet and/or oral hypoglycaemic agents (OHA) but later require insulin treatment. Islet cell antibodies and antibodies to GAD 65 have been associated with the development of insulin deficiency in this group of patients. In the present study, 150 patients with the initial diagnosis of type 2 diabetes mellitus in adulthood (30-60 years) were seen regularly over a period of 5 years in our diabetes outpatient clinic. Though treatment was started with diet or diet plus OHA, insulin therapy had to be introduced in a subset of patients. In all cases, serum obtained at the time of the initial diagnosis was analysed for islet cell antibodies and GAD 65 antibodies, as well as for thyroid and adrenal autoantibodies as possible markers for polyendocrine involvement. Islet cell antibody status, body mass index and the presence of thyroid and adrenal autoantibodies showed no significant correlation to subsequent insulin requirement (< 2 years after diagnosis). In contrast, GAD 65 antibodies were significantly associated with the occurrence of clinical insulin dependency less than 2 years after the initial diagnosis (P < 0.01), thus identifying a substantial proportion of patients requiring insulin therapy within the first 2 years after the diagnosis of type 2 diabetes. Determination of GAD 65 antibodies in patients with late-onset diabetes may contribute to their correct classification and adequate treatment.

Adult↗