Search PubMed⌕ Search

Biomedical subjects

G A Spinas

Publications and source records attributed to G A Spinas.

At least 19 recordsLinked to original sources
PubMed2003

Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.

Adult↗
PubMed2002

[The pathogenesis of type 2 diabetes--new aspects and clinical consequences].

Type 2 diabetes mellitus manifests itself in individuals who lose the ability to produce sufficient quantities of insulin to maintain normoglycemia in the face of insulin resistance. The ability to secrete adequate amounts of insulin depends on beta-cell function and mass. The endocrine pancreas has a remarkable capacity to adapt to conditions of increased insulin demand and only a minority of individuals fail to adapt and become diabetic with time. Secondary events that further reduce the function of beta-cells in type 2 diabetes mellitus are the so-called beta-cell gluco- and lipotoxicity: chronic stimulation of islets by high glucose and free fatty acid levels results in the reduction of insulin secretion. Part of these effects are reversible once these metabolites are normalized and the beta-cell re-exposed to a physiologic environment. The essential role of the beta-cell failure in type 2 diabetes is reminiscent to the pathophysiology of type 1 diabetes. The possible link between both diseases and the therapeutic implications are discussed.

Blood Glucose↗
PubMed2002

[General insulin therapy practice in type 2 diabetes mellitus].

In most patients with Type 2 Diabetes, the primary treatment goal is near-normoglycemia. If diet, physical activity, and oral hypoglycemic agents fail to achieve the individual treatment goal, insulin therapy must be considered. Insulin therapy in patients with Type 2 Diabetes is safe, highly efficient and should be initiated not too late. We recommend to perform the insulin therapy in Type 2 Diabetics individually upon the patients characteristics, no general recommendation can be given. Possible approaches to start an insulin therapy in general practice are discussed. Insulin therapy may be initiated as bedtime insulin (depot insulin at bedtime) in combination with oral agents. In patients who fail to achieve good glycemic control with this combination therapy, mealtime insulin (short-acting insulin before the meals) may be introduced instead of the oral agents (multiple injection regimen). Bedtime insulin may be discontinued when fasting glucose concentrations remain in the desired range and no rise of glucose concentrations occurs during the night. The two-insulin-injection regimen with mixed insulin formulations may be initiated in patients with Type 2 Diabetes when a multiple injection regimen is not feasible. The two-insulin-injection should not be considered as the primary insulin strategy in patients with Type 2 Diabetes.

Delayed-Action Preparations↗
PubMed2002

[Management of cardiovascular risk factors in type 2 diabetes mellitus].

Cardiovascular disease is by far the major cause of morbidity and mortality in subjects with diabetes mellitus type 2. The risk of cardiovascular disease in persons with type 2 diabetes is greater for any given risk factor, alone or in combination, than it is in persons without diabetes. Independent risk factors for cardiovascular disease in type 2 diabetes are hyperglycemia, hypertension, dyslipidemia and smoking. Subjects with diabetes mellitus type 2 benefit from cardiovascular risk factor modification, either as a primary or secondary intervention, as much as or more than those without diabetes. Risk factor modification includes behavioral modification to affect regular physical activity, healthy diet, weight loss, and smoking cessation. In addition, an optimal glycemic control with HbA1c < 7% is crucial and, aggressive management of hypertension (< 130/80 mmHg) and dyslipidemia are particularly important. Finally, aspirin (100 mg/d) is standard in secondary prophylaxis of cardiovascular events and should strongly be considered in primary prophylaxis if subjects have more than 1 concomitant cardiovascular risk factors.

Cardiovascular Diseases↗
PubMed2002

[Practical management of diabetic foot].

Prevention and the correct treatment of the diabetic foot have important social and economic consequences. Risk stratification is essential for choosing the appropriate treatment strategy. History and careful clinical examination identify the risk in each individual patient with diabetes. Peripheral neuropathy (PNP), foot deformation, peripheral arterial disease (PAD) and a history of previous ulcer or amputation are the most important risk factors. PAD must be diagnosed and treated by percutan transluminal angioplasty or bypass surgery where necessary. Primary foot deformation or secondary due to PNP require shoe modifications. Good metabolic control of diabetes and treatment of other cardiovascular risk factors (dyslipidemia, hypertension) delay or prevent the development of PNP and PAD. Therefore an early multidisciplinary approach is essential for each patient with diabetes and foot problems. In the presence of a foot ulcer, it's important to diagnose osteomyelitis by clinical or radiological examination. The choice and duration of antibiotic treatment and surgical intervention depends on the localisation and extension of infection around the ulcer and the presence of osteomyelitis. In case of limb threatening infection, the patient should be referred to a specialized treatment facility immediately.

Arthropathy, Neurogenic↗
PubMed2002

Dietary magnesium intake in type 2 diabetes.

BACKGROUND: Magnesium deficiency is common in type 2 diabetes and may have a negative impact on glucose homeostasis and insulin resistance, as well as on the evolution of complications such as retinopathy, thrombosis and hypertension. OBJECTIVE: To assess the dietary magnesium intake of patients with type 2 diabetes in Zurich, Switzerland and to compare the magnesium intake of diabetic and non-diabetic subjects. DESIGN: The magnesium intake of 97 randomly selected patients with type 2 diabetes and 100 healthy, non-diabetic controls matched for age and sex was estimated using a diet history method. During winter and summer periods, mean daily magnesium intakes were calculated from detailed information given by the test subjects about their eating habits over the previous 2 months. The calculations were performed using EBIS, a computer program based on a German nutrient data base (BLS 2.3), with food items specific to Switzerland added or directly analysed when necessary. RESULTS: The mean+/-s.d. daily magnesium intake of the male diabetic and male control subjects was 423.2+/-103.1 and 421.1+/-111.0 mg, respectively. The mean daily magnesium intake of the female diabetic and female control subjects was 419.1+/-109.7 and 383.5+/-109.7 mg, respectively. There were no significant differences in daily magnesium intake between the diabetic and the non-diabetic subjects and mean intakes in both groups exceeded Swiss recommended dietary intakes. CONCLUSIONS: Dietary intake of magnesium appears sufficient in Swiss adults with type 2 diabetes and is unlikely to contribute to the aetiology of magnesium deficiency. SPONSORSHIP: The Swiss Federal Institute of Technology, Zurich, Switzerland.

Adult↗
PubMed2002

A plasma glucose concentration below 2.5 mmol L-1 is not an appropriate criterion to end the 72-h fast.

CONTEXT: The classical end-point to terminate the 72-h fast in a patient evaluated for a hypoglycaemic disorder is the occurrence of hypoglycaemic symptoms in association with a low plasma glucose level. However, neither the symptoms nor the plasma glucose level have been exactly defined. OBJECTIVE: To determine whether a useful cut-off plasma glucose concentration as criterion to end the prolonged fast in the absence of neuroglycopenic symptoms can be defined. DESIGN: Single centre case-control study. SETTING: Tertiary referral hospital in Switzerland. SUBJECTS: The 72-h fast was prospectively performed in 23 consecutive patients (17 women and six men) following a standardized protocol between July 1999 and January 2002. All patients were referred to our clinic for evaluation of suspected hypoglycaemia. The criterion to end the fast before 72 h was defined by the occurrence of symptoms or signs typical for neuroglycopenia irrespective of plasma glucose levels. MAIN OUTCOME MEASURE: Insulin levels and insulin to plasma glucose ratios in insulinoma patients and in individuals without insulin-secreting tumours at termination of the fast and at plasma glucose levels </=2.5 mmol L-1, prior to the occurrence of neuroglycopenic symptoms. RESULTS: In seven patients, the fast was terminated before 72 h because they developed neuroglyco-penic symptoms. Insulin-secreting tumours were found and successfully removed in these seven patients. Sixteen individuals developed no neuroglycopenic symptoms throughout the 72-h fast and an insulin-secreting tumour could be excluded in these 16 patients. Five of these 16 individuals had plasma glucose levels </=2.5 mmol L-1 during the 72-h fast. Insulin levels and insulin to glucose ratios in insulinoma patients and healthy individuals overlapped during as well as at termination of the fast. Prior to the occurrence of neuroglycopenic symptoms and at venous plasma glucose </=2.5 mmol L-1, insulin to plasma glucose ratios dropped in insulinoma patients to values within the normal range on several occasions. CONCLUSIONS: Terminating the fast at plasma glucose levels </=2.5 mmol L-1 does not allow confirmation or exclusion of an insulin-secreting tumour. Thus, the occurrence of symptoms or signs typical for neuroglycopenia is the prerequisite criterion to end the fast before 72 h.

Adolescent↗
PubMed2001

10 Swiss kindreds with multiple endocrine neoplasia type 1: assessment of screening methods.

PRINCIPLES: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease characterised by the combined occurrence of tumours of the parathyroid glands, the enteropancreatic neuroendocrine system and the anterior pituitary gland. The genetic defect has been mapped to the long arm of chromosome 11q13, and the MEN1-gene was recently identified by positional cloning. Genetic screening for MEN1 germline mutations allows the identification of gene carriers in affected kindreds. Biochemical and radiological screening for MEN1 tumours allows an earlier diagnosis and treatment, and, thus may reduce morbidity and mortality. Since there is no consensus about the frequency and the extent of the necessary screening investigations, evaluation of proposed screening programs is of importance. METHODS: The aims of our study were to identify the MEN1-gene mutations and to detect the gene-carriers in 10 Swiss MEN1 families, as well as to assess biochemical and radiological screening methods. The study included 45 members from 10 MEN1 families. RESULTS: Every family had a different type of MEN1-gene mutation. Thirty out of 45 family members were gene mutation carriers. Twenty-two MEN1-gene carriers had typical MEN1 tumours: parathyroid, enteropancreatic and pituitary tumours were found in 21, 14 and 1 patients, respectively. Applying a defined screening program the following manifestations in asymptomatic MEN1-gene carriers were detected: 9 primary hyperparathyroidism, 3 nonfunctioning pancreatic tumours, 1 gastrinoma, 1 nonfunctioning microadenoma of the pituitary and 1 macronodular adrenal hyperplasia. CONCLUSIONS: The genetic screening facilitates the identification of individuals who carry MEN1-gene mutations, and allows one to exclude non-mutant gene carriers from further investigations. The prospective biochemical and radiological screening of gene mutation carriers allows the earlier detection of MEN1-associated tumours. Therefore, it might be expected that morbidity and mortality of the MEN1 could be reduced.

Adolescent↗
PubMed2001

Economic and clinical impact of alternative disease management strategies for secondary prevention in type 2 diabetes in the Swiss setting.

PRINCIPLES: Different intervention strategies for the optimisation of disease management of diabetes exist and have been shown to increase the proportion of patients receiving screening and examinations and to improve risk factors such as HbA1c, lipids, and blood pressure. Thus, in the long-term, a decrease in diabetic complications and the associated costs could be expected. To address this question, the current analysis used a published diabetes simulation model to analyse the long-term clinical and economic implications of implementing various interventions in the Swiss setting. METHODS: Based on data from the literature, the short-term effects on clinical variables of multifactorial interventions, including screening for nephropathy and retinopathy, educational programmes and control of cardiovascular risk profile were assessed, and a cost-effectiveness analysis in comparison to standard care was performed. Life expectancy (LE) and total lifetime costs (TC) from the perspective of the health insurance payer were calculated using a long-term Markov simulation model. RESULTS: The multifactorial intervention led to an improvement in undiscounted LE of 0.56 years (LE = 10.73 and 11.29 years for standard care and multifactorial intervention respectively), and a reduction in 3%-discounted TC of CHF 7313 (10.7%) per patient compared to current standard practice. Extrapolation to the whole Swiss type 2 diabetes population (285,000) showed yearly cost savings of CHF 194 million from the multifactorial intervention. CONCLUSIONS: The implementation of multifactorial interventions, including improved control of cardiovascular risk factors, combined with early diagnosis and treatment of diabetic complications, could be both cost- and life-saving in the Swiss setting.

Complementary Therapies↗
PubMed2001

Clinical and technical evaluation of a new self-monitoring blood glucose meter: assessment of analytical and user error.

Our study aimed to validate (against the standards of the American Diabetes Association and the International Organization for Standardization) the analytical and clinical accuracy of the new MediSense Precision Plus Electrodes on the QID system when compared with a reference method using the Abbott Vision glucose analyzer. Previous studies have shown that the overall accuracy of the device also depends on the proficiency of the operator, so we also assessed the 'ease of use' of the MediSense system, by comparing the results obtained by the patient and health care professional. Accuracy of the self-monitored blood glucose measurements was evaluated over a wide range of glucose readings (2.6-20.0 mmol/l). Between-run CVs (using the manufacturer's quality control material) were found to be 7% at 2.7 mmol/l and 4.8% at 15.5 mmol/l (n=380). We used the error-grid analysis with target range blood glucose, then separated the data into different subsets. We found that 100% of all measurements were in the clinically acceptable zones of A and B. All measured values of the MediSense QID system complied with the requirements for 'blood glucose monitoring meters', as proposed by the International Organization for Standardization. The rating of the patient questionnaire showed a good to very good overall rating and acceptance with a short instruction time. The results indicate that that the MediSense QID/Precision Plus Electrodes is a reliable and easy to use device, which can be recommended for the majority of patients with diabetes mellitus.

Adult↗
PubMed2001

Assessment of selective arterial calcium stimulation and hepatic venous sampling to localize insulin-secreting tumours.

OBJECTIVE: Non-invasive localization modalities such as ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) often fail to localize insulinomas smaller than 2 cm in diameter. Recent studies have shown that the selective arterial stimulation and hepatic venous sampling (ASVS) technique using intra-arterial calcium as the insulin secretagogue facilitates the regionalization of such occult insulinomas. This study assesses the sensitivity of ASVS in localizing insulin-secreting tumours. SUBJECTS AND METHODS: Eleven consecutive patients (8 women), aged 29-82 years, were studied over the past 4 years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin-secreting tumour was proven in all patients. Calcium gluconate (0.025 mEq/kg body weight) was injected directly into the arteries supplying the pancreas and the liver. Insulin levels were measured in samples taken from the right hepatic vein before and 30, 60 and 120 s after each injection. The ASVS technique was performed in all 11 patients; the results were compared with the surgical findings in 10 patients and the autopsy findings in 1 case. The ASVS results were also compared with the findings of other, previously performed imaging modalities. RESULTS: ASVS correctly localized 4 insulin-secreting tumours to the head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1 to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological examination), sized 4-25 mm, were found in 10 patients. All were cured by selective surgery and remained free of hypoglycaemia over the next 1-4 years of follow-up. An insulin-secreting neuroendocrine tumour in the liver was documented in 1 case at autopsy. CONCLUSIONS: Arterial stimulation and hepatic venous sampling is a very sensitive technique for preoperative localization of insulin-producing tumours. It can help to plan minimally invasive surgery and to select an appropriate strategy for patients suffering from malignant tumours in others.

Adult↗
PubMed2001

Alterations of lipolytic enzymes and high-density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus.

OBJECTIVE: This study investigates the effects of regular moderate physical activity on lipolytic enzymes and plasma lipid concentration, particularly high-density lipoprotein cholesterol (HDL-C) subfractions, in patients with type 2 diabetes mellitus. DESIGN: Ten patients participated in a 3-month exercise programme without any changes in current medical therapy. The control group consisted of six patients who were matched with regard to sex, age, diabetes duration and diabetes therapy. RESULTS: Mean (+/- SE) physical activity in the intervention group increased from 70 +/- 21 to 220 +/- 28 min per week, which resulted in an increase in total HDL-C from 1.04 +/- 0.07 to 1.28 +/- 0.12 (P < 0.001). The HDL3-C subfraction increased from 0.71 +/- 0.08 to 0.86 +/- 0.08 mM (P = 0.01) with no significant changes in the HDL2-C subfraction (0.33 +/- 0.04 vs. 0.42 +/- 0.05). These changes were paralleled by an 85% increase in hepatic lipase (HL) activity, from 25.7 +/- 5.1 to 47.4 +/- 4.9 micromol x mL(-1) x h(-1) (P < 0.001) and a 45% increase in lipoprotein lipase (LPL) activity, from 16.8 +/- 3.0-24.3 +/- 2.7 micromol x mL(-1) x h(-1) (P = 0.01). Lecithin-cholesterol acyl-transferase (LCAT) activity increased by 32%, from 156 +/- 26 to 206 +/- 32 nmol x mL(-1) x h(-1) (P < 0.001). In the control group there were no significant changes in any of the variables assessed. CONCLUSIONS: Regular moderate physical activity in patients with type 2 diabetes led to an overall increase in HL, LPL, and LCAT. HL showed a more pronounced increase than LPL and LCAT. The changes in lipolytic and transferase enzyme pattern resulted in a significant increase of plasma HDL-C, mainly of the HDL3-C subfraction.

Adult↗
PubMed2001

Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function.

Glucotoxicity and lipotoxicity contribute to the impaired beta-cell function observed in type 2 diabetes. Here we examine the effect of saturated and unsaturated fatty acids at different glucose concentrations on beta-cell proliferation and apoptosis. Adult rat pancreatic islets were cultured onto plates coated with extracellular matrix derived from bovine corneal endothelial cells. Exposure of islets to saturated fatty acid (0.5 mmol/l palmitic acid) in medium containing 5.5, 11.1, or 33.3 mmol/l glucose for 4 days resulted in a five- to ninefold increase of beta-cell DNA fragmentation. In contrast, monounsaturated palmitoleic acid alone (0.5 mmol/l) or in combination with palmitic acid (0.25 or 0.5 mmol/l each) did not affect DNA fragmentation. Increasing concentrations of glucose promoted beta-cell proliferation that was dramatically reduced by palmitic acid. Palmitoleic acid enhanced the proliferation activity in medium containing 5.5 mmol/l glucose but had no additional effect at higher glucose concentrations (11.1 and 33.3 mmol/l). The cell-permeable ceramide analog C2-ceramide mimicked both the palmitic acid-induced beta-cell apoptosis and decrease in proliferation. Moreover, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on beta-cell viability. Additionally, palmitic acid but not palmitoleic acid decreased the expression of the mitochondrial adenine nucleotide translocator and induced release of cytochrome c from the mitochondria into the cytosol. Finally, palmitoleic acid improved beta-cell-secretory function that was reduced by palmitic acid. Taken together, these results suggest that the lipotoxic effect of the saturated palmitic acid involves an increased apoptosis rate coupled with reduced proliferation capacity of beta-cells and impaired insulin secretion. The deleterious effect of palmitate on beta-cell turnover is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway. In contrast, the monounsaturated palmitoleic acid does not affect beta-cell apoptosis, yet it promotes beta-cell proliferation at low glucose concentrations, counteracting the negative effects of palmitic acid as well as improving beta-cell function.

Animals↗
PubMed2001

Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets.

In autoimmune type 1 diabetes, Fas-to-Fas-ligand (FasL) interaction may represent one of the essential pro-apoptotic pathways leading to a loss of pancreatic beta-cells. In the advanced stages of type 2 diabetes, a decline in beta-cell mass is also observed, but its mechanism is not known. Human islets normally express FasL but not the Fas receptor. We observed upregulation of Fas in beta-cells of type 2 diabetic patients relative to nondiabetic control subjects. In vitro exposure of islets from nondiabetic organ donors to high glucose levels induced Fas expression, caspase-8 and -3 activation, and beta-cell apoptosis. The effect of glucose was blocked by an antagonistic anti-Fas antibody, indicating that glucose-induced apoptosis is due to interaction between the constitutively expressed FasL and the upregulated Fas. These results support a new role for glucose in regulating Fas expression in human beta-cells. Upregulation of the Fas receptor by elevated glucose levels may contribute to beta-cell destruction by the constitutively expressed FasL independent of an autoimmune reaction, thus providing a link between type 1 and type 2 diabetes.

Adolescent↗
PubMed2001

Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes.

Several studies support the concept of a diabetic cardiomyopathy in the absence of discernible coronary artery disease, although its mechanism remains poorly understood. We investigated the role of glucose and palmitic acid on cardiomyocyte apoptosis and on the organization of the contractile apparatus. Exposure of adult rat cardiomyocytes for 18 h to palmitic acid (0.25 and 0.5 mmol/l) resulted in a significant increase of apoptotic cells, whereas increasing glucose concentration to 33.3 mmol/l for up to 8 days had no influence on the apoptosis rate. However, both palmitic acid and elevated glucose concentration alone or in combination had a dramatic destructive effect on the myofibrillar apparatus. The membrane-permeable C2-ceramide but not the metabolically inactive C2-dihydroceramide enhanced apoptosis of cardiomyocytes by 50%, accompanied by detrimental effects on the myofibrils. The palmitic acid-induced effects were impaired by fumonisin B1, an inhibitor of ceramide synthase. Sphingomyelinase, which activates the catabolic pathway of ceramide by metabolizing sphingomyeline to ceramide, did not adversely affect cardiomyocytes. Palmitic acid-induced apoptosis was accompanied by release of cytochrome c from the mitochondria. Aminoguanidine did not prevent glucose-induced myofibrillar degeneration, suggesting that formation of nitric oxide and/or advanced glycation end products play no major role. Taken together, these results suggest that in adult rat cardiac cells, palmitic acid induces apoptosis via de novo ceramide formation and activation of the apoptotic mitochondrial pathway. Conversely, glucose has no influence on adult cardiomyocyte apoptosis. However, both cell nutrients promote degeneration of myofibrils. Thus, gluco- and lipotoxicity may play a central role in the development of diabetic cardiomyopathy.

Animals↗
PubMed2001

Diminished insulin secretory response to glucose but normal insulin and glucagon secretory responses to arginine in a family with maternally inherited diabetes and deafness caused by mitochondrial tRNA(LEU(UUR)) gene mutation.

OBJECTIVE: The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes. RESEARCH DESIGN AND METHODS: The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test. RESULTS: The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099). CONCLUSIONS: This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Adult↗
PubMed2000

Applying some UK Prospective Diabetes Study results to Switzerland: the cost-effectiveness of intensive glycaemic control with metformin versus conventional control in overweight patients with type-2 diabetes.

OBJECTIVE: The results of the metformin substudy of the United Kingdom Prospective Diabetes Study (UKPDS) were applied through modelling techniques to the Swiss setting, allowing a cost-effectiveness analysis of the management of overweight type-2 diabetes patients with either conventional glycaemic control or intensive control with metformin from the Swiss third-party payer perspective. METHODS: Occurrence of diabetes-related complications was simulated using a Markov model. Probabilities for complications were taken from the UKPDS, and costs were retrieved from published sources. Total direct costs (costs of diabetes therapy plus costs of treating complications) and survival over an 11-year period were determined for cohorts randomised to either conventional glycaemic control or intensive control with metformin. Changes in life expectancy were calculated for conventional versus intensive control with metformin. Extensive sensitivity analysis was performed. RESULTS: Mean costs per patient over the 11-year follow-up period (discounted at 5% per annum) were CHF 10,877 and CHF 9950 for patients randomised to either conventional control or intensive control with metformin respectively. Intensive control with metformin led to improved survival (0.43 life-years gained per patient) over the 11-year-period. Outcomes were most sensitive to variations in the acquisition costs of metformin. Changes in the event rates and costs related to myocardial infarction, renal failure, and stroke also had important impacts. CONCLUSIONS: Within the limitations of the modelling study, intensive glycaemic control with metformin was cost- and life-saving in overweight type-2 diabetes patients in the Swiss setting.

Blood Glucose↗