A longitudinal study of fear of hypoglycaemia in adults with type 1 diabetes.

AIMS: To investigate fear of hypoglycaemia (FoH) longitudinally in a cross-sectional study of adult patients with type 1 diabetes. Specifically, we investigated two subgroups of patients who over 4 years either showed a substantial increase or decrease in level of FoH to identify factors associated with changes in FoH. METHODS: The Swedish version of the Hypoglycaemia Fear Survey (HFS) along with a questionnaire to assess hypoglycaemia history was sent by mail to 764 patients in 2010. The responders in 2010 (n = 469) received another set of the same two questionnaires in 2014. HbA1c, insulin regimen, weight and creatinine from 2010 and 2014 were obtained from medical records. Those with an absolute difference in HFS scores ≥ 75th percentile were included in the subgroup analyses. Statistical analyses included one-sample t tests, chi-square and McNemar's test. RESULTS: The absolute difference in the HFS total score (n = 347) between 2010 and 2014 was m = ±7.6, SD ± 6. In the increased FoH group, more patients reported a high level of moderate hypoglycaemic episodes as well as impaired awareness of hypoglycaemia in 2014 compared with the decreased FoH group. There were more subjects in the increased FoH group with insulin pumps in 2014 and in 2010. In the decreased FoH group, more patients had a high frequency of daily self-monitoring of blood glucose (SMBG) in 2010 and in 2014. CONCLUSIONS: Fear of hypoglycaemia is stable across time for most patients. Changes in fear level are associated with changes in hypoglycaemia frequency. Thus, asking patients about changes in hypoglycaemia experiences is of great importance.

Skin microvascular function in patients with type 1 diabetes: An observational study from the onset of diabetes.

BACKGROUND: The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. MATERIAL AND METHODS: Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. RESULTS: Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p < 0.01). PRH% was lower than in the reference group after 7-9 years ( p < 0.01), and lower than baseline after 24-29 years of diabetes ( p < 0.05). All but one patient developed retinopathy and the first signs were found after 10 years of diabetes. CONCLUSIONS: Functional disturbances in total skin microcirculation were observed after seven years in patients with type 1 diabetes and preceded diabetic complications such as retinopathy.

Impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes.

AIMS: The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia. METHODS: Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a randomised, double-blind, cross-over study. Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Various biochemical markers of endothelial function were also investigated. RESULTS: Endothelium-dependent microvascular reactivity decreased during atorvastatin (p < 0.001), showing a significant treatment effect compared with placebo (p = 0.04). Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45% to 7.77% (p = 0.008). CONCLUSIONS: The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes, thus implicating a risk for deterioration of microvascular function during such therapy in these patients.

Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: a mass spectrometric and isotope labeling study.

Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent - a phenomenon called "aspirin resistance". We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to "aspirin resistance" in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5-10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the α-chain: αK191, αK208, αK224, αK429, αK457, αK539, αK562, in the ß-chain: ßK233, and in the γ-chain: γK170 and γK273. Glycations were found at ßK133 and γK75, alternatively γK85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [(14)C-acetyl]salicylic acid and [(14)C]glucose, a labeling of 0.013-0.084 and 0.12-0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9-100 µM aspirin) and physiologically (2-8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of fibrinogen. This may mechanistically explain why aspirin facilitates fibrin degradation. We find no support for the idea that glycation of fibrin(ogen) interferes with acetylation of fibrinogen.

High-dose aspirin is required to influence plasma fibrin network structure in patients with type 1 diabetes.

OBJECTIVE: Patients with type 1 diabetes form a less permeable fibrin network, which could contribute to their increased risk of cardiovascular disease (CVD). Low-dose aspirin treatment is the standard in the management of CVD; however, the effect seems reduced in patients with diabetes. We investigated the effects of low- and high-dose aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim) and the possible interaction between the treatment effects of aspirin on fibrin network permeability and glycemic control in these patients (secondary aim). RESEARCH DESIGN AND METHODS: Forty-eight patients (24 subjects with good [HbA(1c) <7.4%] and 24 subjects with poor [HbA(1c) >8.4%] glycemic control) were randomly assigned to treatment with 75 or 320 mg/day aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated the treatment periods. The plasma fibrin network was assessed by determination of the permeability coefficient (K(s)). RESULTS: Treatment with 75 mg aspirin did not influence fibrin network permeability (K(s)). However, K(s) increased significantly during treatment with 320 mg aspirin (P = 0.004), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009). The increase in K(s) during high-dose aspirin treatment was significant in patients with poor glycemic control (P = 0.02), whereas K(s) only tended to increase in patients with good glycemic control (P = 0.06). CONCLUSIONS: A high dose of aspirin is required to influence fibrin network permeability in patients with type 1 diabetes. The observed lack of effect with low-dose aspirin may contribute to aspirin treatment failure in diabetes.

Analyte flux at a biomaterial-tissue interface over time: implications for sensors for type 1 and 2 diabetes mellitus.

OBJECTIVE: The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). METHOD: Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose. RESULTS: Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device. CONCLUSIONS: Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM.

Basal insulin substitution with glargine or continuous subcutaneous insulin infusion in adult type 1 diabetes patients-a randomized controlled trial.

BACKGROUND: It is generally held that basal insulin substitution with continuous subcutaneous insulin infusion (CSII) provides less variable glucose levels than with long-acting insulin analogs, e.g., glargine, in patients with type 1 diabetes, although this has not been convincingly demonstrated by continuous glucose monitoring. METHODS: To compare glucose control assessed by a continuous glucose monitoring system (CGMS) during basal insulin substitution with glargine versus CSII, we conducted a non-blinded, randomized, crossover trial in 15 type 1 diabetes patients experienced with CSII. All subjects were randomly assigned to receive either a morning dose of insulin glargine, comprising their average 24-h basal insulin requirement, minus 2.4 U, which was delivered by the pump, or to continue as before for 4 weeks followed by a 1-week washout period and a crossover. All mealtime doses of insulin were given by the pump as before. CGMS data were blinded until the end of the study. RESULTS: The mean blood glucose was lower in the non-glargine arm according to self-monitoring of plasma glucose (9.2 vs. 10.6 mmol/L; P = 0.010) and CGMS (9.1 vs. 10.3 mmol/L; P = 0.002), and hemoglobin A1c was 6.5% without glargine versus 6.8% with (P = 0.018). There were no significant differences in glucose variability measured as SD of plasma glucose (SDPG) or mean amplitude of glycemic excursions (MAGE), although significantly longer periods of glucose values spent within the target of 4.5-10.0 mmol/L were demonstrated in the non-glargine arm using CGMS (P = 0.034). More episodes below 3.5 mmol/L were seen during the CSII period (P = 0.053). CONCLUSIONS: CSII provided improved glucose control compared to glargine with a lower mean plasma glucose and longer periods of glucose values within target on a somewhat lower insulin dose. There was a tendency with more episodes below 3.5 mmol/L during CSII. No difference with respect to glucose variability was found when calculated as SDPG or MAGE.

Atorvastatin has antithrombotic effects in patients with type 1 diabetes and dyslipidemia.

INTRODUCTION: Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia. MATERIALS AND METHODS: Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured. RESULTS: During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001). CONCLUSIONS: Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.

A cognitive behavior therapy-based intervention among poorly controlled adult type 1 diabetes patients--a randomized controlled trial.

OBJECTIVE: To examine the impact of a Cognitive Behavior Therapy (CBT)-based intervention on HbA(1c), self-care behaviors and psychosocial factors among poorly controlled adult type 1 diabetes patients. METHODS: Ninety-four type 1 diabetes patients were randomly assigned to either an intervention group or a control group. The intervention was based on CBT and was mainly delivered in group format, but individual sessions were also included. All subjects were provided with a continuous glucose monitoring system (CGMS) during two 3-day periods. HbA(1c), self-care behaviors and psychosocial factors were measured up to 48 weeks. RESULTS: Significant differences were observed with respect to HbA(1c) (P<0.05), well-being (P<0.05), diabetes-related distress (P<0.01), frequency of blood glucose testing (P<0.05), avoidance of hypoglycemia (P<0.01), perceived stress (P<0.05), anxiety (P<0.05) and depression (P<0.05), all of which showed greater improvement in the intervention group compared with the control group. A significant difference (P<0.05) was registered with respect to non-severe hypoglycemia, which yielded a higher score in the intervention group. CONCLUSION: This CBT-based intervention appears to be a promising approach to diabetes self-management. PRACTICE IMPLICATIONS: Diabetes care may benefit from applying tools commonly used in CBT. For further scientific evaluation in clinical practice, there is a need for specially educated diabetes care teams, trained in the current approach, as well as cooperation between diabetes care teams and psychologists trained in CBT.

Experience from a behavioural medicine intervention among poorly controlled adult type 1 diabetes patients.

AIM: To describe experience from a behavioural medicine intervention among poorly controlled adult type 1 diabetes patients, in terms of feasibility, predictors and associations of improved glycaemic control. METHODS: Data were collected on 94 poorly controlled adult type 1 diabetes patients who were randomised to a study evaluating the effects of a behavioural medicine intervention. Statistics covered descriptive and comparison analysis. Backward stepwise regression models were used for predictive and agreement analyses involving socio-demographic and medical factors, as well as measures of diabetes self-efficacy (DES), diabetes locus of control (DLOC), self-care activities (SDSCA), diabetes-related distress (Swe-PAID-20), fear of hypoglycaemia (HFS), well-being (WBQ), depression (HAD) and perceived stress (PSS). RESULTS: The participation rate in the study was 41% and attrition was 24%. Of those patients actually participating in the behavioural medicine intervention, 13% withdrew. From the regression models no predictors or associations of improvement in HbA(1c) were found. CONCLUSIONS: The programme proved to be feasible in terms of design and methods. However, no clear pattern was found regarding predictors or associations of improved metabolic control as the response to the intervention. Further research in this area is called for.

Psychometric evaluation of the Swedish version of the Hypoglycaemia Fear Survey.

OBJECTIVE: The objective of this study was to evaluate the psychometric properties of the Swedish version of the Hypoglycaemia Fear Survey (Swe-HFS) for use among Swedish-speaking patients with type 1 diabetes. METHODS: The HFS was translated using the forward-backward translation method and was thereafter answered by 325 type 1 patients. The psychometric properties were investigated using exploratory factor analysis, Cronbach's alpha, content and convergent validity. RESULTS: The factor analysis showed that a three-factor solution was reasonable with the subscales Behaviour/Avoidance (10 items), Worry (6 items) and Aloneness (4 items). Cronbach's alpha coefficient for the total score was 0.85. The result also supports the instrument's content validity and convergent validity. CONCLUSION: The Swedish version of the HFS appears to be a reliable and valid instrument for measuring fear of hypoglycaemia (FoH) in type 1 patients. PRACTICE IMPLICATIONS: The results from this study suggest that the Swe-HFS, an instrument that is brief and easy to administer, may be valuable in clinically assessing FoH among patients with type 1 diabetes.

The psychometric properties of the Swedish version of the Problem Areas in Diabetes Scale (Swe-PAID-20): scale development.

BACKGROUND: Considering the importance of psychological aspects in the management of diabetes, there is a need of validated measurements in this area. Such tools make it possible to screen patients for specific conditions as well as they serve as reliable measures when evaluating medical, psychological and educational interventions. OBJECTIVES: The current study was conducted to adapt the Problem Areas in Diabetes Scale for use among Swedish-speaking patients with type 1 diabetes and to evaluate the psychometric properties. DESIGN: Methodological research design was used in this study. SETTING AND PARTICIPANTS: A convenience sample of 325 type 1 diabetes patients was systematically selected from the local diabetes registry of a university hospital in Stockholm, Sweden. METHODS: Following the linguistic adaptation using the forward-backward translation method, the 20-item PAID was answered by the selected patients. Statistics covered exploratory factor analysis, Cronbach's alpha, convergent validity and content validity. RESULTS: In the factor analysis a three-factor solution was found to be reasonable with the sub-dimensions diabetes-related emotional problems (15 items), treatment-related problems (2 items) and support-related problems (3 items). Cronbach's alpha coefficient for the total score was 0.94 and varied between 0.61 and 0.94 in the three subscales. The findings also gave support for the convergent and content validity. CONCLUSIONS: The Swedish version of the Problem Areas in Diabetes Scale (Swe-PAID-20) seems to be a reliable and valid outcome for measuring diabetes-related emotional distress in type 1 diabetes patients.

Patient management of long-term continuous subcutaneous insulin infusion.

AIM: This paper reports a study of patients' current practice with continuous subcutaneous insulin infusions, particularly with respect to the management of the pump. BACKGROUND: Successful implementation of continuous subcutaneous insulin infusion requires a motivated patient with a range of technical skills and self-management capabilities. The therapy should be prescribed, implemented and monitored by a skilled professional team familiar with it and capable of supporting the patient. METHODS: A questionnaire was mailed to 102 continuous subcutaneous insulin infusion treated patients at a Swedish university hospital with experience of pump treatment for at least 6 months. RESULTS: The questionnaire was answered by 88% of the patients, 53 women and 37 men, aged 22-71 years with a duration of continuous subcutaneous insulin infusion use of between 7 months and 19 years. The changing interval for soft infusion set ranged from 2.0 to 10.0 days (mean 4.8) and for metal needles from 1.5 to 7.5 days (mean 3.8), P = 0.001. Catheter occlusions were significantly more often reported in patients with presence of bleeding at the infusion site (P = 0.011) and among those using insulin lispro (P = 0.032). CONCLUSIONS: Patients having long-term continuous subcutaneous insulin infusion should be carefully audited with respect to the management of the insulin pump and its accessories. In patients who frequently experience problems, shorter intervals between changes of infusion sets are strongly advocated and type of insulin preparation may be of importance in some cases.

[The National Diabetes Registry 1996-2003. Quality assessment shows improved diabetic care]. / Nationella diabetesregistret 1996-2003. Kvalitetsvärdering visar att diabetesvården har förbättrats.

The Swedish National Diabetes Register presents results during the period 1996-2003. Quality of care data from more than 75,000 diabetic patients (2003) treated at medical departments and primary health care centres are evaluated concerning national goals of HbA1c < 6.5% and BP < 140/85 mm Hg, the prevalence of lipid treatment, smoking etc. The national goals of HbA1c and BP were reached with increasing degree in cross-sectional analysis during the period, and were achieved by 33% and 71% at medical departments, and by 61% and 48% in primary health care in 2003. A similar tendency was also seen in longitudinal analysis of subgroups 1996-2003. The use of antihypertensive and lipid-lowering drugs was also considerably increased. This should imply a reduction of the risk for diabetic complications. As the national goals are still difficult to reach, individual goals should be set for the treatment.

Intensive therapy with inhaled insulin via the AERx insulin diabetes management system: a 12-week proof-of-concept trial in patients with type 2 diabetes.

OBJECTIVE: To compare the glycemic control of inhaled insulin via the AERx insulin diabetes management system (iDMS) with that of subcutaneous (SC) insulin, both combined with NPH insulin at bedtime, in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The AERx iDMS uses a liquid insulin formulation to achieve flexible precise mealtime dosing (with increments corresponding to 1 IU administered subcutaneously) and ensures insulin delivery only when the breathing technique is optimal. This trial in patients with type 2 diabetes compared the glycemic control (HbA(1c)) achieved by inhaled insulin administered via AERx iDMS with that using SC insulin. This was a randomized, 12-week, open-label, parallel, multicenter, multinational trial in 107 nonsmoking patients with type 2 diabetes (mean age 59 years, mean duration of diabetes 11.9 years). Patients were randomized to receive either inhaled fast-acting human insulin via AERx iDMS immediately before meals or SC fast-acting human insulin administered 30 min before meals, both in combination with evening NPH insulin. RESULTS: Baseline and demographic characteristics were similar between the two groups. There was no statistically significant difference in HbA(1c) between the AERx and SC groups after 12 weeks of treatment (7.84 +/- 0.77 vs. 7.76 +/- 0.77%, P = 0.60). Fasting serum glucose was significantly lower in the AERx group compared with the SC group by the end of the trial (8.9 +/- 3.8 vs. 10.8 +/- 3.7 mmol/l, P = 0.01) with a similar NPH dose in the two groups (0.23 vs. 0.23 IU/kg, P = 0.93). There were no statistically significant differences between the two groups in the intra-subject variability of fasting or prandial blood glucose increment. Adverse events were similar in the two groups. No major safety concerns were raised during the trial. CONCLUSIONS: In patients with type 2 diabetes, preprandial inhaled insulin via AERx iDMS is as effective as preprandial SC insulin injection in achieving glycemic control with similar tolerability.

[Episodes of severe hypoglycemia--increasing problem in type 1 diabetes]. / Tillbud av allvarlig hypoglykemi--ökande problem vid diabetes typ 1.

A cross-sectional survey of severe hypoglycaemia was performed in type 1 diabetes mellitus patients in 1984 and repeated in 1998 at the diabetes out-patient clinic of a Swedish university hospital. The study revealed that the prevalence of severe hypoglycaemia had increased by more than 50 per cent over 14 years, in spite of more frequent use of multiple insulin injection therapy and daily self monitoring of blood glucose. A multiple logistic regression analysis of risk factors for severe hypoglycaemia explained less than 10% of the variance, implicating only unawareness of hypoglycaemia and HbA1c. It is concluded that long duration type 1 diabetes mellitus patients are increasingly vulnerable with respect to severe hypoglycaemia and that this should be taken into account when individual treatment goals are being proposed to patients. Novel short-acting and long-acting analogs of insulin as well as insulin pumps may prove useful to minimize the risk of severe hypoglycaemic episodes. It is argued that the ability of currently marketed glucose monitoring systems to sensitively and specifically detect hypoglycaemia is limited.

Alteration of the counterregulatory responses to insulin-induced hypoglycemia and of cognitive function after massive weight reduction in severely obese subjects.

The autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis are reported as activated in excess in the morbidly obese state and, therefore, changes after weight loss can be anticipated. The aim of this study was to investigate the impact of a massive (approximately 30%) weight reduction on the activation of the HPA axis and the ANS following bariatric surgery. Eight (7 women, 1 man) severely obese (125+/-12 kg; body mass index [BMI], 45+/-4 kg/m2) nondiabetic subjects, underwent a 3-hour hyperinsulinemic (1,034 pmol/kg/h) glucose clamp study at hypoglycemia of arterial B-glucose concentration of 3.4 mmol/L. Cognitive function was evaluated by a visuospatial computerized problem-solving test, the Perceptual Maze Test (PMT). The mean weight loss was 40+/-9 kg approximately 12 months postsurgery when their weight was stabilized (85+/-6 kg; BMI, 31+/-3 kg/m2), and insulin sensitivity improved to an average increase of 376%+/-250% (P<.01) of initial value. Before weight reduction, all patients demonstrated brisk peak responses in glucagon, epinephrine, pancreatic polypeptide (PP), norepinephrine, and cortisol, indicative of preserved or exaggerated activation of ANS and HPA axis. In the reduced-obese state, all these responses were attenuated and most markedly so for glucagon, which was totally abolished. In contrast, the growth hormone (GH) response was increased after weight reduction. The cognitive function was clearly modified by weight reduction both during normoglycemia and hypoglycemia and was changed preferentially to a speed-preferring strategy in the reduced-obese state compared with a more accuracy preferred problem-solving process of PMT test presurgery. These results demonstrate a reduction of the glucose counterregulatory hormonal responses, increased insulin sensitivity, and perturbed cognitive function after massive weight reduction. It may be speculated on if the increased insulin sensitivity and reduced counterregulation to hypoglycemia could predispose to low plasma glucose concentrations.

Improved beta-cell function after standardized weight reduction in severely obese subjects.

Islet function was examined in 13 severely obese women [body mass index 46.4 +/- 5.5 (SD) kg/m(2)] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR(1)), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37-50% after 15 and 25% WR (P