Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial.

AIM: To confirm the superiority, compared with placebo, of adding liraglutide to pre-existing basal insulin analogue ± metformin in adults with inadequately controlled type 2 diabetes [glycated haemoglobin (HbA1c) 7.0-10.0% (53-86 mmol/mol)]. METHODS: In this 26-week, double-blind, parallel-group study, conducted in clinics or hospitals, 451 subjects were randomized 1 : 1 to once-daily liraglutide 1.8 mg (dose escalated from 0.6 and 1.2 mg/day, respectively, for 1 week each; n = 226) or placebo (n = 225) added to their pre-existing basal insulin analogue (≥20 U/day) ± metformin (≥1500 mg/day). After randomization, insulin adjustments above the pre-study dose were not allowed. The primary endpoint was HbA1c change. RESULTS: After 26 weeks, HbA1c decreased more with liraglutide [-1.3% (-14.2 mmol/mol)] than with placebo [-0.1% (-1.2 mmol/mol); p < 0.0001]. More subjects on liraglutide reached HbA1c targets: <7.0% (59% vs 14%; p < 0.0001) and ≤6.5% (43% vs 4%; p < 0.0001) using slightly less insulin (35.8 IU vs 40.1 IU). Greater decreases from baseline (estimated treatment differences vs placebo; p < 0.0001) occurred in fasting plasma glucose (-1.3 mmol/l), seven-point glucose profiles (-1.6 mmol/l), body weight (-3.1 kg) and systolic blood pressure (-5.0 mmHg). Transient gastrointestinal adverse events (nausea: 22.2% vs 3.1%) and minor hypoglycaemia (18.2% vs 12.4%) were more frequent with liraglutide than placebo, and pulse increased (4.5 beats/min) compared with placebo. No severe hypoglycaemia or pancreatitis occurred. CONCLUSIONS: Adding liraglutide to a basal insulin analogue ± metformin significantly improved glycaemic control, body weight and systolic blood pressure compared with placebo. Typical gastrointestinal symptoms and minor hypoglycaemia were more frequent with liraglutide.

Self-reported non-severe hypoglycaemic events in Europe.

AIMS: Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self-reported non-severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin-treated Type 2 diabetes mellitus. METHODS: People in seven European countries aged >15 years with Type 1 diabetes or insulin-treated Type 2 diabetes (basal-only, basal-bolus and other insulin regimens) were recruited via consumer panels, nurses, telephone recruitment and family referrals. Respondents completed four online questionnaires. The first questionnaire collected background information on demographics and hypoglycaemia-related behaviour, whilst all four questionnaires collected data on non-severe hypoglycaemic events in the preceding 7 days. RESULTS: Analysis was based on 11 440 respondent-weeks from 3827 respondents. All participants completed the first questionnaire and 57% completed all four. The mean number of events/respondent-week was 1.8 (Type 1 diabetes) and 0.4-0.7 (Type 2 diabetes, with different insulin treatments) corresponding to annual event rates of 94 and 21-36, respectively. A total of 63% of respondents with Type 1 diabetes and 49-64% of respondents with Type 2 diabetes, treated with different insulin regimens, who experienced hypoglycaemic events, reported impaired hypoglycaemia awareness or unawareness. A high proportion of respondents rarely or never informed their general practitioner/specialist about hypoglycaemia: 65% (Type 1 diabetes) and 50-59% (Type 2 diabetes). Overall, 16% of respondents with Type 1 diabetes and 26% of respondents with Type 2 diabetes reported not being asked about hypoglycaemia during routine appointments. CONCLUSION: Non-severe hypoglycaemic events are common amongst people with Type 1 diabetes and insulin-treated Type 2 diabetes in real-world settings. Many rarely or never inform their general practitioner/specialist about their hypoglycaemia and the real burden of hypoglycaemia may be underestimated.

Lethal evolution of a newborn with consistent features of hydrolethalus syndrome--Romanian patient.

Hydrolethalus syndrome is a severe lethal disorder most commonly found in Finland. We present a lethal case of complex congenital malformation in a Romanian family who showed multiple signs described in hydrolethalus syndrome. Our case presented the specific characteristics: macrocephaly, midline cleft-lip, cleft palate, polydactyly of both hands and feet but without occipitoschisis, considered as the pathognomonic sign of the syndrome. Sequencing analysis of HYLS1 did not identify the point mutation present in the Finnish cases or other mutations in this gene.

Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects.

The reduction in blood glucose in non-insulin-dependent diabetes mellitus (NIDDM) brought about by the use of phenobarbital (PB), a hepatic microsomal enzyme inducer, suggests an improvement in insulin sensitivity. The effect of PB on insulin-mediated glucose metabolism was hence investigated using the euglycemic clamp technique in 10 women with NIDDM aged 56-75 yr. The addition of PB to sulfonylurea therapy, concurrently for 6 wk, reduced fasting blood glucose (BG, from 12.8 +/- 1.6 to 10.2 +/- 3.2 mmol/L, P less than 0.01) and immunoreactive insulin (IRI) levels (from 32.4 +/- 13.6 to 24.7 +/- 9.8 mU/L, P less than 0.01), whereas body weight remained unaltered. During the trial, there was a significant change in the glucose disposal rate (M, from 1.27 +/- 0.60 to 2.82 +/- 0.86 mg/kg/min, P less than 0.001), the metabolic clearance rate of glucose (from 0.89 +/- 0.41 to 2.24 +/- 1.27 ml/kg/min, P less than 0.01), the insulin sensitivity index (from 1.10 +/- 0.44 to 2.86 +/- 1.54 mg/kg/min: mU/L X 100, P less than 0.001), and the plasma antipyrine clearance rate (from 28.3 +/- 11.7 to 51.4 +/- 20.2 ml/min, P less than 0.001), an in vivo index of liver microsomal enzyme activity. The antipyrine clearance rate correlated with insulin-mediated glucose metabolism (r2 = 0.560, P less than 0.01). This correlation could be interpreted as indicating that, in NIDDM patients, peripheral glucose utilization and the liver microsomal enzyme system share common regulators. Our study suggests a new approach to the improvement of insulin sensitivity in NIDDM patients.

Fetal hemoglobin in diabetic patients.

OBJECTIVE: To determine the occurrence of elevated fetal hemoglobin (HbF) among the diabetic population and determine the clinical situation of importance. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted. HbA1c and HbF were measured with high-performance liquid chromatography in 1,104 consecutive diabetic patients attending our clinic for HbA1c determination. The expression of clinical correlations between the high and low HbF group was performed for adults (> or = 15 years). A nondiabetic control group (n = 258) with the same age and sex distribution was included. RESULTS: HbF was elevated (> 1.0% of total hemoglobin) in 7.5% of the total diabetic group. In the adult diabetic group, HbF was elevated in 6.5% of the patients, and in the control group, HbF was elevated in 1.9% (P < 0.01). In the insulin-treated adult group, HbF was elevated in 10.2% of the patients, and in the non-insulin-treated group, HbF was elevated in 3.8%. The mean HbA1c was 8.90 +/- 2.00% among the patients and 5.52 +/- 0.53% in the control subjects (P < 0.001). Patients with elevated HbF were younger (P < 0.02) and more often on insulin therapy (P < 0.001) or type I diabetic patients (P < 0.001). Sex, glycemic control, or duration of diabetes were not significantly different in the patients with high or low HbF. Correlation was not detected between the amount of HbF and HbA1c or age in the group of patients with elevated HbF. Hemoglobinopathies, anemias, or malignancies were not diagnosed from the patients with high HbF. CONCLUSIONS: Level of HbF is increased (> 1.0%) among 7.5% of unselected diabetic patients. In adult (> or = 15 years) diabetic patients, it is increased among 6.5%, which is 3.4 times more often than in the control population. Acute hematological conditions or malignancies do not explain the difference. Elevated HbF seems to be associated with type I diabetes and insulin treatment.

Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. A case report.

OBJECTIVE: To evaluate the efficacy of the insulin analog lispro (Lys B28, Pro B29) in severe insulin resistance caused by human insulin antibodies. CASE: A 27-year-old man with a history of diabetes treated with human insulin for 3 years developed severe immunological insulin resistance caused by human insulin antibodies. Throughout follow-up (12 months) the insulin analog lispro was administered with an infusion pump as the only insulin therapy. The insulin dose decreased from an average of 300 U/day to 58 U/day, HbA1c decreased from 12.6 to 7.4%, and human insulin antibodies decreased from 8,057 to 1,860 nU/ml. Hypoglycemic episodes during early morning disappeared. CONCLUSIONS: The insulin analog lispro might be suitable for the treatment of diabetic patients with substantially increased insulin antibody levels Apparently, the structural difference between the lispro and human insulin molecules prevented lispro from binding to the human insulin antibodies in this patient and consequently was nonimmunogenic.

Fibrotic process and drug metabolism in alcoholic liver disease.

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.

Serum N-terminal atrial natriuretic peptide in adult patients late after surgical repair of atrial septal defect.

BACKGROUND: The purpose of surgical closure of atrial septal defect (ASD) is to relieve the cardiovascular system from a haemodynamic burden. Excessive amounts of atrial peptides are released in congestive heart failure, valvular diseases and congenital heart diseases. AIMS: To examine whether patients after surgical repair of ASD have higher concentrations of N-terminal atrial natriuretic peptide (ANP-N) than age-, sex- and body mass index (BMI)-matched control subjects. METHODS: Medical history, physical examination, standard 12-lead electrocardiogram, and ANP-N concentrations were obtained in 65 adult patients operated for ASD at the age of 21+/-13 years (mean+/-standard deviation), 21+/-6 years after surgical closure of ASD. Sixty-seven healthy subjects matched for age, sex and BMI served as controls. RESULTS: In the patients serum ANP-N was higher than in the control subjects 0.41+/-0.32 nmol/l, median 0.31 nmol/l, interquartile range (IQR) 0.21-0.49 nmol/l vs. 0.24+/-0.12 nmol/l, median 0.23 nmol/l, IQR 0.17-0.29 nmol/l, (P=0.0003). Patients with concomitant diseases had higher ANP-N concentrations (0.51+/-0.39 nmol/l, median 0.34, IQR 0.26-0.73 nmol/l) than ASD patients without any history or signs of disease (0.28+/-0.16 nmol/l, median 0.27, IQR 0.17-0.40 nmol/l, P=0.01). The 'healthy' ASD patients had higher hormone concentrations than age-, sex- and BMI-matched control subjects (0.28+/-0.16 median 0.27 nmol/l, IQR 0. 17-0.40 nmol/l and 0.21+/-0.07 nmol/l, median 0.20 nmol/l, IQR 0. 15-0.27 nmol/l, P=0.01). Multiple stepwise linear regression analysis showed that age at operation was strongly associated with the post-operative ANP-N concentration (r(2)=0.25, P=0.0002). CONCLUSION: ASD patients have higher ANP-N concentrations late after surgical repair. Hormone levels correlate with age at operation. Our finding supports the clinical praxis of operating on these patients in their childhood and adolescence.

Does uremia interfere with HbA1c results in the FPLC method with Mono S cation exchanger?

To study the effect of uremia on hemoglobin A1c determination by the Mono S FPLC method, samples from uremic patients, with and without diabetes, and controls, were analysed with a modified chromatography with enhanced resolution. Besides specific HbA1c, four minor peaks could be seen, included in routine HbA1c values. Two of these differed in concentration in the patient groups studied: a shoulder-like peak close to the specific HbA1c (S fraction) and a slightly less cationic minor peak (M fraction). Both S and M peaks were higher in uremic than in nonuremic subjects, but the M peak was associated more with diabetes. In the nondiabetic group, the mean routine HbA1c value was 0.8% units higher in uremic than nonuremic individuals. The specific HbA1c was nondependent on uremia. Thus, in uremic patients, there seems to be falsely elevated HbA1c values, mainly because of small interfering hemoglobin fractions, not specific HbA1c.

Effect of acetaldehyde and acetylsalicylic acid on HbA1c chromatography in the FPLC method with Mono S cation exchanger.

The effects of alcohol and aspirin on HbA1c chromatography in the Mono S method were studied in vitro and in vivo. A modified chromatography with enhanced resolution was used, making possible detailed examination of minor interfering peaks included in the routine HbA1c value. Incubation with acetylsalicylic acid increased a hemoglobin fraction separate from HbA1c. In vivo this fraction was elevated by 0.1% of the total hemoglobin during therapeutic aspirin ingestion for one month. In vitro acetaldehyde generated two labile hemoglobin fractions and slightly increased a minor stable fraction which was also elevated in vivo in both alcoholics and heavy drinkers. In relation to the HbA1c concentration, this stable fraction was equal in both alcoholic groups. We conclude that the in vivo effects of both aspirin and alcohol are negligible in routine HbA1c determination. Factors other than acetaldehyde might account for the unexpected HbA1c values in alcoholics.

Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice.

We aim to evaluate the effects of phenobarbital (PB) on the liver drug metabolism, NADPH production capacity and terminal gluconeogenic enzyme, glucose-6-phosphatase (G6Pase) activity in the diabetic state associated with genetic obesity in mice. The results showed that PB treatment increased the amount of liver total cytochrome P450 (cytP450), a drug metabolizing monooxygenase enzyme in genetically obese, hyperglycemic (ob/ob) mice 6-fold and the total activities of other monooxygenase enzymes NADPH cytP450 reductase and 7-ethoxyresorufin O-deethylase (ERDE) 2- and 6.5-fold, respectively. In addition, the regimen increased the liver total activities of two NADPH generating enzymes, 6-phosphogluconate dehydrogenase (6PGDH) and malic enzyme (ME) in obese mice suggesting that the regimen enhanced liver NADPH production capacity in the animals. The data further showed that PB treatment decreased the high hepatic G6Pase activity in obese mice. Both enhanced NADPH generating enzyme activities and lowered G6Pase activity may suppress hepatic glucose output. Since NADPH is required for drug oxidation reactions as a reducing cofactor, high NADPH generating capacity may facilitate liver drug metabolism in vivo. Although the diabetic state in obese mice differs somewhat from that seen in non-insulin dependent diabetic subjects (NIDDs), these findings provide some knowledge about the possible biochemical mechanisms whereby PB treatment normalizes drug metabolism and glycemic control in NIDDs, as has been noted in previous studies.

Natriuretic peptide and echocardiography after operation of atrial septal defect.

Patients benefit from surgical seclusion of atrial septal defect but have excessive cardiovascular morbidity after the operation. We evaluated haemodynamics and looked for abnormalities of cardiac structures and function late after surgical seclusion of the defect. Serum N-terminal natriuretic peptide measurement and transthoracic and transoesophageal echocardiography were performed in 61 patients aged 43+/-15 years (mean+/-standard deviation) 21+/-5 years after surgery. The findings were compared with 67 control subjects. The patients had higher serum N-terminal atrial natriuretic peptide concentration than the control subjects (0.40+/-0.32 vs. 0.24+/-0.12 nmol/l, P=0.0001). Peptide levels correlated with current age (P=0.0001) and age at operation (P=0.0014), but not with age in the control subjects. In the patients, echocardiography measurements of cardiac dimensions correlated with hormone levels (atrial natriuretic peptide concentration with left atrial end-systolic diameter (P=0.042), left ventricular end-diastolic (P=0.021) and end-systolic diameter (P=0.042). There were only 10 patients (16%) without any abnormality in echocardiography. Their peptide concentration was 0.25+/-0.18 nmol/l (P=not significant compared to the control subjects). The association between increasing N-terminal atrial peptide levels and operation age together with echocardiography findings support the clinical consensus of treating atrial septal defect patients in their childhood and adolescence.

Pulmonary involvement in nephropathia epidemica: radiological findings and their clinical correlations.

Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome (HFRS) normally taking a benign clinical course. The etiologic agent, Puumala hantavirus is genetically closely related to Sin Nombre virus, which causes a frequently lethal febrile syndrome with pulmonary involvement (hantavirus pulmonary syndrome, HPS). HPS is characterized by acute respiratory distress, non-cardiogenic pulmonary edema and severe and hypotension, but usually no significant renal involvement. Pulmonary involvement and respiratory symptoms also occur in NE. To understand the mechanisms of pulmonary involvement in NE, we studied the clinical records and chest X-rays of 125 hospital-treated acutely ill NE patients. Twenty-eight percent of the patients had disease-related changes in their chest radiographs. Pleural effusion and atelectasis were the most common X-ray findings, whereas frank pulmonary edema was rare. The patients with pathologic X-ray findings had a more marked hypoproteinemia (lowest measured serum protein concentration 54 +/- 1 g/l) than those with normal X-ray (62.1 +/- 0.9 g/l, p < 0.001) and leukocytosis (highest measured blood leukocyte count 14.1 +/- 0.9 x 10(9)/l vs. 10.6 +/- 0.6 x 10(9)/l, p < 0.001) and more severe renal insufficiency (highest measured serum creatinine 590 +/- 60 mumol/l vs. 356 +/- 29 mumol/l, p < 0.05). Hypoproteinemia best predicted the occurrence of abnormal chest X-ray findings in NE. This suggests, that capillary leakage and inflammation may play a role in the pathogenesis of NE lung involvement, similarly as in HPS. Differently from HPS, the fluid volume overload associated with renal insufficiency seemed to contribute strongly to the chest X-ray changes in NE.

Effects of celiprolol on insulin sensitivity and glucose tolerance in dyslipidemic hypertension.

The effects of celiprolol on insulin sensitivity, glucose tolerance and serum lipids were compared to those of other antihypertensive drugs (beta- or Ca-blocker or ACE-inhibitor) in 23 dyslipidemic non-diabetic patients with controlled hypertension. Hyperinsulinemic euglycemic clamp and independent oral glucose tolerance tests (OGTT) were performed before and 6 months after the study treatment. Six patients out of 23 were randomized to the control group where antihypertensive monotherapy was kept unchanged. Mean glucose disposal rate (M, mean +/- SEM) determined in the clamp test increased in the celiprolol group from 24.4 +/- 2.3 to 34.9 +/- 2.4 mumol/kg/min (p < 0.001). Insulin sensitivity improved during celiprolol treatment independent of the previous treatment. In the control group, M remained practically unchanged (21.6 +/- 3.7 mumol/kg/min). During 2 h OGTT, incremental glucose and insulin AUC decreased in the celiprolol group from 4.5 +/- 0.7 to 2.0 +/- 0.6 mM*h (p < 0.002) and from 113 +/- 16 to 72 +/- 10 mU/l*h (p < 0.005), respectively. There was also a small beneficial change in serum lipids in the celiprolol group: a reduction in serum total cholesterol (-4%), triglycerides (-11%) and LDL-cholesterol (-9%), and an increase in HDL-cholesterol (+6%) and HDL/LDL ratio (+15%). No significant change occurred in the control group. Fasting serum glucose and insulin did not change significantly in either group. In this study with a limited control group, celiprolol improved insulin sensitivity, glucose tolerance and serum lipid profiles of dyslipidemic hypertensive patients.

Work conditions and accidents in three industries.

Four studies conducted in the light metal, electrotechnical and printing industries are described. The purpose was to determine the applicability of the systems approach to occupational accidents. The data consisted of 291 accidents and 701 controls. The stable characteristics of the workers or the environments were not good predictors of accidents. The clearest differences between the accidents and the controls involved the worker's situational experience, the frequency of task occurrence, the familiarity of the tasks, and the mobility of dangers. The complexity of the information exchange between man and his environment, as well as the perceptibility of environmental dangers, contributed to the occurrence of accidents.

Subcutaneous and intraperitoneal insulin therapy in diabetic patients on CAPD.

We evaluated in a cross-over manner the consequences of subcutaneously and intraperitoneally given insulin on glucose control, insulin sensitivity, and serum lipids in 8 type I diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The patients were treated with both subcutaneous and intraperitoneal insulin for at least three months. After each period, metabolic studies were performed. Despite significantly improved glycemic control (Hb A1c 10.00 +/- 0.38% after subcutaneous and 8.40 +/- 0.36% after intraperitoneal insulin, p = 0.01), serum lipids showed unfavorable changes. High-density lipoprotein (HDL)-cholesterol was significantly lower (1.28 +/- 0.18 mmol/L vs 0.88 +/- 0.06 mmol/L, p = 0.03) and low-density lipoprotein (LDL)/HDL-cholesterol ratio was higher (p = 0.025) during intraperitoneal insulin. Total cholesterol, LDL-cholesterol, and triglycerides were higher during intraperitoneal insulin administration. Severe hypoglycemic episodes were more common during subcutaneous than intraperitoneal insulin. It is concluded that, although intraperitoneal insulin administration offers significantly better glycemic control and insulin sensitivity than subcutaneous insulin, the effect of serum lipids is more disadvantageous possibly via a direct effect of insulin on the liver.

Intraperitoneal insulin reduces plasma leptin concentration in diabetic patients on CAPD.

OBJECTIVE: To determine the effects of subcutaneous (SC) and intraperitoneal (IP) insulin on serum leptin concentration in type I diabetic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective, open, before-after study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Twelve type I diabetic patients with stabilized CAPD, age 43.9 +/- 2.8 years, and duration of diabetes 30.4 +/- 3.5 years. INTERVENTION: After stabilized CAPD therapy, all patients were treated first with SC insulin for a median of 3 months, and thereafter with IP insulin for another 3 months. MAIN OUTCOME MEASURES: Plasma leptin, insulin sensitivity with euglycemic clamp, and glycemic and uremic status after both treatment periods. RESULTS: During SC insulin therapy, plasma leptin concentration was significantly higher than during IP insulin (19.8 +/- 5.9 ng/mL and 12.8 +/- 6.2 ng/mL, respectively; p < 0.001). Leptin concentration was higher in CAPD patients and was related to body mass index in both genders. No correlation was detected between plasma leptin and fasting insulin, glycemic control, glucose disposal rate, or serum lipids. CONCLUSION: Plasma leptin concentration is lower during IP insulin therapy compared to SC insulin. Insulin has probably a direct effect on both peritoneal leptin clearance and adipose tissue leptin production. The significance of leptin in regulating appetite and anorexia in uremia remains unclear.

High peritoneal permeability predisposes to hepatic steatosis in diabetic continuous ambulatory peritoneal dialysis patients receiving intraperitoneal insulin.

OBJECTIVE: To evaluate hepatic fat accumulation in diabetic patients taking intraperitoneal or subcutaneous insulin treatment during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Cross-sectional study. SETTING: Tertiary-care university hospital. PATIENTS: We studied 16 patients with diabetic end-stage renal disease currently treated with CAPD. Median age was 42 years (range: 34-70 years), duration of diabetes was 27.5 years (range: 17-39 years), and duration of CAPD was 16.5 months (range: 2-59 months). OUTCOME MEASURES: Ultrasound measures of liver steatotic area and thickness, peritoneal equilibration test (PET), weekly Kt/V urea, protein catabolic rate (PCR), hemoglobin A1c (HbA1c), lipoproteins, alanine aminotransferase, alkaline phosphatase, insulin dose, and dialysate glucose load. RESULTS: Focal hepatic fat accumulation was found. The location of steatosis was subcapsular; a negligible amount was periportal. Hepatic subcapsular steatosis was present in 7 of 8 patients taking insulin intraperitoneally and in 0 of 8 patients taking insulin subcutaneously. The maximal thickness of subcapsular steatosis correlated directly with peritoneal transport rate (2-hour dialysate-to-plasma creatinine ratio in PET, r = 0.80, p < 0.05) and inversely with PCR (r = -0.82, p < 0.05). The area of the lesions correlated directly with body weight (r = 0.80, p < 0.05) and inversely with weekly Kt/V urea (r = -0.90, p < 0.01). CONCLUSIONS: Intraperitoneal insulin, together with glucose-based peritoneal dialysate, induces hepatic subcapsular steatosis. The amount of hepatic subcapsular steatosis increases when peritoneal transfer rate and body weight are high.

The effect of insulin delivery route on lipoproteins in type I diabetic patients on CAPD.

OBJECTIVE: To evaluate the influence of subcutaneous and intraperitoneal (i.p.) insulin on plasma lipoproteins in type I diabetic (IDDM) patients with end-stage renal failure (ESRD) treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A before-after trial. SETTING: University hospital outpatient care. PARTICIPANTS: Eleven IDDM patients with stabilized peritoneal dialysis, age 42.9 +/- 2.9 (SEM) years and duration of diabetes 31.4 +/- 3.4 years. INTERVENTION: Two treatment periods during stabilized CAPD. All patients were first treated with subcutaneous and then with i.p. insulin. The studies were performed after a median time of 3 months on each treatment. MAIN OUTCOME MEASURES: Plasma lipids; apoproteins (Apo) A-I, A-II, and B; high-density lipoprotein (HDL) subfractions; glycemic status; and uremic status. RESULTS: After changing from subcutaneous insulin to i.p. insulin, plasma HDL cholesterol decreased (from 1.29 +/- 0.13 mmol/L to 0.96 +/- 0.06 mmol/L, p < 0.05), and the low density to high density lipoprotein (LDL/HDL) cholesterol ratio increased (p < 0.05). The HDL cholesterol decreased in both HDL2 and HDL3 fractions, but significantly so only in HDL3 (p < 0.01). ApoA-I (p < 0.05) decreased while the ApoB/ApoA-I ratio (p < 0.01) and the ApoA-I/HDL-cholesterol ratio (p < 0.01) increased during i.p. insulin therapy. Intraperitoneal insulin resulted in significantly better glycemic control than subcutaneous insulin (p < 0.01). CONCLUSIONS: In diabetic patients on CAPD therapy, i.p. insulin, although inducing better glycemic control than subcutaneous insulin, was associated with lowered plasma HDL cholesterol and ApoA-I levels. The atherogenic potential is probably less than expected as the relative particle size of HDL remained unchanged.

Charcot arthropathy of the diabetic foot. Current concepts and review of 36 cases.

BACKGROUND AND AIMS: The incidence of diabetic Charcot neuroarthropathy has increased. The purpose here was to study the current diagnostics and treatment of the Charcot foot. MATERIALS AND METHODS: During a time period from 1994 to 2000, a total of 36 feet were diagnosed as cases of diabetic Charcot neuroarthropathies. A retrospective analysis of patient records and radiographs was undertaken. A review of the recent literature is presented. RESULTS: 29 cases were diagnosed in the dissolution stage, 2 in coalascence, and 5 in the resolution stage. The diagnostic delay averaged 29 weeks. Treatment with cast immobilisation ranged from 4 to 37 weeks (mean 11 weeks). A total of 14 surgical procedures were carried out on 10 patients: six exostectomies, four midfoot arthrodeses, one triple arthrodesis, one tibiocalcaneal arthrodesis and two below-knee amputations. A radiological fusion was achieved in two thirds of the attempted arthrodeses. CONCLUSIONS: A physician should always consider the Charcot neuroarthropathy when a diabetic patient has an inflamed foot. In the absence of fever, elevated CRP or ESR, infection is a highly unlikely diagnosis, and a Charcot process should primarily be considered. The initial treatment of an inflamed Charcot foot consists in sufficiently long non-weightbearing with a cast, which should start immediately after the diagnosis. The prerequisites of successful reconstructive surgery are correct timing, adequate fixation and a long postoperative non-weightbearing period. In the resolution stage most Charcot foot patients need custom-molded footwear.